bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrogallol impairs staphylococcal biofilm formation via induction of bacterial oxidative stress
Authors: Roese Katharina H C , Torlone Christina , Cooper Lauren A , Esposito Lee , Deveau Amy M , Röse Ursula S R , Burkholder Kristin M
Published: November 2023

Aims

To examine the effect of the phenolic compound pyrogallol on staphylococcal biofilm formation.

Methods and results

In crystal violet biofilm assays, pyrogallol-reduced biofilm formation in Staphylococcus epidermidis ATCC 35984, Staph. epidermidis NRRL-B41021, Staphylococcus aureus USA300, and Staph. aureus Newman, without significantly impairing bacterial viability. Pyrogallol-mediated impairment of biofilm formation was likely due to induction of bacterial oxidative stress, as its effect was greater in catalase-deficient versus WT Staph. aureus, and biofilm production was rescued by exogenous catalase. The effect of pyrogallol on staphylococcal biofilm formation mirrored that of the known oxidant hydrogen peroxide, which also reduced biofilm formation in a dose-dependent manner.

Conclusions

Pyrogallol reduces biofilm formation in S. aureus and Staph. epidermidis in a mechanism involving induction of bacterial oxidative stress.
Breast Imaging Fellowship Virtual Interviews: The Program Director’s Perspective
Authors: Katzen Janine , Nguyen Jonathan , Zuckerman Samantha , Wang Lilian , Whitman Gary , Mango Victoria
Published: November 2023

Objective

To evaluate breast imaging fellowship program directors’ perspectives on the virtual interview process.

Methods

A 20-question survey constructed by members of the Fellowship Match Committee of the Society of Breast Imaging was distributed to all 99 breast imaging program directors registered with the Society. An initial e-mail with a link to the survey was distributed on September 9, 2022, and the survey was closed on October 1, 2022. Results were compiled and a descriptive statistical analysis was performed utilizing Microsoft Excel.

Results

There were 63 total responses (63/99, 64% response rate). There was a wide distribution in both the number of applications received and the number of interviews each program offered. Just under a fifth (12/63, 19%) of programs received 1 to 5 applications, whereas a quarter (16/63, 25%) received over 40 applications. In contrast, over a quarter (17/63, 27%) of programs interviewed 1 to 5 applicants, and only a small number (3/63, 5%) interviewed over 40 applicants. When reporting what worked best with the virtual interview process, the responses fell into the following 4 categories: efficiency, flexibility, virtual format, or other. When reporting what did not work well, the most common response (14/37, 38%) was conveying the atmosphere of the program in the virtual setting.

Conclusion

This study provides an assessment of the virtual interview experience from the perspective of breast imaging fellowship programs, which may be useful in optimizing future interview experiences for programs and applicants.
Making Right to Housing Work: Learnings from YUVA’s Approach of Enabling the Right to Adequate Housing
Authors: Joseph Marina , Siddharth K J , Jaikishen Doel
Published: November 2023

This article presents a model of human rights practice in India, specifically focused on the right to adequate housing for marginalized groups. It details this through the praxis of a 40-year-old non-profit organization called Youth for Unity and Voluntary Action (YUVA). The article presents the approach, rooted in the specific socio-legal contexts of Indian cities where YUVA works. Four key elements from YUVA’s model of work are elaborated: a) facilitating access to citizenship rights to enable individual claim-making; b) formation of people’s organizations towards collectivization; c) formation of wider city- and state-level alliances towards policy and advocacy shifts; d) strategic inputs to drive inclusion in urban plans. Although the insights embody the experience of a single organization, they offer several lessons for wider human rights practice with respect to realizing the right to housing in developing country contexts, especially in the Global South.
Low risk of erectile dysfunction after nontransecting bulbar urethroplasty for urethral stricture: a systematic review and meta-analysis
Authors: Zhao Xingming , Xing Yanbo , Zhang Xi , Guo Qiang , Li Chengyong , Guo Chao , Wang Jingqi , Hao Chuan
Published: November 2023

Background

Sexual function after urethroplasty may be a concern for patients, but there are still some controversies regarding the consequences of nontransecting bulbar urethroplasty (ntBU) in terms of erectile dysfunction (ED).

Aim

This meta-analysis aimed to compare the efficacy and safety of ntBU with that of transecting bulbar urethroplasty (tBU).

Methods

The PubMed, Web of Science, Cochrane, and Embase databases were searched and reviewed up to October 31, 2022. Quality evaluation was performed using the Newcastle-Ottawa scale system and Cochrane tools for the nonrandomized and randomized studies, respectively. Baseline characteristics, preoperative information, and postoperative outcomes were collected.

Outcomes

Outcomes included success rate, ED, overall complication, and maximum urinary flow.

Results

Thirteen studies comprising 1683 patients met the inclusion criteria, with 596 and 1087 patients undergoing ntBU and tBU, respectively. The results revealed that compared with the tBU group, the patients who underwent ntBU had a significantly lower incidence of ED, while there were no significant differences in the other perioperative outcomes. In subgroup analysis, the nontransecting anastomotic urethroplasty group had a lower incidence of ED than excision and primary anastomosis, and other perioperative outcomes were similar between the 2 groups.

Clinical implications

The results of the study may help clinicians choose procedures that protect sexual function in the treatment of urethral stricture.

Strengths and limitations

The strength of this study is that it is, to our knowledge, the first meta-analysis to evaluate the efficacy and safety of ntBU. A limitation is that most of the included studies were retrospective cohort studies.

Conclusion

ntBU preserves the high efficacy of its transecting counterpart while reducing postoperative ED.
Arabidopsis PHYTOALEXIN DEFICIENT 4 promotes the maturation and nuclear accumulation of immune-related cysteine protease RD19
Authors: Zeng Yanhong , Zheng Zichao , Hessler Giuliana , Zou Ke , Leng Junchen , Bautor Jaqueline , Stuttmann Johannes , Xue Li , Parker Jane E , Cui Haitao
Published: November 2023

Arabidopsis PHYTOALEXIN DEFICIENT 4 (PAD4) has an essential role in pathogen resistance as a heterodimer with ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1). Here we investigated an additional PAD4 role in which it associates with and promotes the maturation of the immune-related cysteine protease RESPONSIVE TO DEHYDRATION 19 (RD19). We found that RD19 and its paralog RD19c promoted EDS1- and PAD4-mediated effector-triggered immunity to an avirulent Pseudomonas syringae strain, DC3000, expressing the effector AvrRps4 and basal immunity against the fungal pathogen Golovinomyces cichoracearum. Overexpression of RD19, but not RD19 protease-inactive catalytic mutants, in Arabidopsis transgenic lines caused EDS1- and PAD4-dependent autoimmunity and enhanced pathogen resistance. In these lines, RD19 maturation to a pro-form required its catalytic residues, suggesting that RD19 undergoes auto-processing. In transient assays, PAD4 interacted preferentially with the RD19 pro-protease and promoted its nuclear accumulation in leaf cells. Our results lead us to propose a model for PAD4-stimulated defense potentiation. PAD4 promotes maturation and nuclear accumulation of processed RD19, and RD19 then stimulates EDS1–PAD4 dimer activity to confer pathogen resistance. This study highlights potentially important additional PAD4 functions that eventually converge on canonical EDS1–PAD4 dimer signaling in plant immunity.
The origin of the metallicity distributions of the NE and W stellar shelves in the Andromeda Galaxy
Authors: Milošević S , Mićić M , Lewis G F
Published: November 2023

Tidal streams and stellar shells are naturally formed in galaxy interactions and mergers. The Giant Stellar Stream (GSS), the North-East (NE), and Western (W) stellar shelves observed in Andromeda Galaxy (M31) are examples of these structures and were formed through the merger of M31 and a satellite galaxy. Recent observational papers have provided strong evidence that the shells and GSS originate from a single progenitor. In this paper, we investigate the formation of these two stellar shelves and the detailed nature of their relationship to the GSS. We present numerical simulations of tidal disruption of a satellite galaxy assuming that it is a progenitor of the GSS and the shell system. We represent the progenitor as a dwarf spheroidal galaxy with the stellar mass of 109 M⊙ and evolve its merger with M31 for 3 Gyr to reproduce the chemodynamical properties of the NE and W shelves. We find that an initial metallicity of the progenitor with a negative radial gradient of ΔFeH  = −0.3 ± 0.2 successfully reproduces observed metallicities of the NE, W shelves, and the GSS, showing that all these structures can originate from the same merger event.
The spatially resolved star formation history of the dwarf spiral galaxy NGC 5474
Authors: Bortolini G , Cignoni M , Sacchi E , Tosi M , Annibali F , Pascale R , Bellazzini M , Calzetti D , Adamo A , Dale Daniel A , Fumagalli M , Gallagher John S , Grasha K , Johnson Kelsey E , Linden Sean T , Messa M , Östlin G , Sabbi E , Wofford A
Published: November 2023

We study the resolved stellar populations and derive the star formation history of NGC 5474, a peculiar star-forming dwarf galaxy at a distance of ∼7 Mpc, using Hubble Space Telescope Advanced Camera for Surveys data from the Legacy Extragalactic UV Survey (LEGUS) programme. We apply an improved colour–magnitude diagram fitting technique based on the code sfera and use the latest PARSEC–COLIBRI stellar models. Our results are the following. The off-centre bulge-like structure, suggested to constitute the bulge of the galaxy, is dominated by star formation (SF) activity initiated 14 Gyr ago and lasted at least up to 1 Gyr ago. Nevertheless, this component shows clear evidence of prolonged SF activity (lasting until ∼10 Myr ago). We estimate the total stellar mass of the bulge-like structure to be (5.0 ± 0.3) × 108 M⊙. Such a mass is consistent with published suggestions that this structure is in fact an independent system orbiting around and not within NGC 5474’s disc. The stellar overdensity located to the South–West of the bulge-like structure shows a significant SF event older than 1 Gyr, while it is characterized by two recent peaks of SF, around ∼10 and ∼100 Myr ago. In the last Gyr, the behaviour of the stellar disc is consistent with what is known in the literature as ‘gasping’. The synchronized burst at 10–35 Myr in all components might hint to the recent gravitational interaction between the stellar bulge-like structure and the disc of NGC 5474.
A phenomenological wobbling model for isolated pulsars and the braking index
Authors: Araujo E C A , De Lorenci V A , Peter P , Ruiz L S
Published: November 2023

An isolated pulsar is a rotating neutron star possessing a very high magnetic dipole moment, thus providing a powerful radiating mechanism. These stars loose rotational energy E through various processes, including a plasma wind originating from a highly magnetized magnetosphere and the emission of magnetic dipole radiation (MDR). Such phenomena produce a time decreasing angular velocity Ω(t) of the pulsar that is usually quantified in terms of its braking index. Although these mechanisms are widely acknowledged as the primary drivers of the spin evolution of isolated pulsars, it is plausible that other contributing factors influencing this effect have yet to be comprehensively investigated. Most of young isolated pulsars present a braking index different from that given by the MDR and plasma wind processes. Working in the weak field (Newtonian) limit, we take in this work a step forward in describing the evolution of such a system by allowing the star’s shape to wobble around an ellipsoidal configuration as a backreaction effect produced by its rotational deceleration. It is assumed that an internal damping of the oscillations occurs, thus introducing another form of energy loss in the system, and this phenomenon may be related to the deviation of the braking index from the models based on $\dot{E} \sim -\Omega ^4$ predictions. Numerical calculations suggest that the average braking index for typical isolated pulsars can be thus explained by a simple phenomenological model.
Primordial black hole mass function with mass gap
Authors: Bi Xiao-Ming , Chen Lu , Wang Ke
Published: November 2023

Primordial black holes (PBHs) are mainly characterized by their mass function, in which there may be some huge suppression for certain mass spans. If this is the case, the absence of these PBHs will form mass gaps. In this paper, we investigate the PBH mass function with the mass gap. First, to obtain a data-supported PBH mass function with the mass gap for subsolar masses PBHs, we fine-tune the coefficients of a model-independent power spectrum of primordial curvature perturbations. Then we take this unique PBH mass function into consideration and calculate the energy-density spectrum of the stochastic gravitational-wave background from PBH mergers. We find the location of its first peak almost has no relationship with the mass gap and is only determined by the probability distribution of frequencies at which PBH binaries merge. Apart from the first peak, there must be an accompanying smaller trough at a higher frequency resulting from the mass gap. Therefore, the detection of this smaller trough will provide more information about inflation and PBH formation.
Nitrogen abundances of the Be-type stars in 30 Doradus
Authors: Dufton P L , Langer N , Lennon D J , Schneider F R N , Evans C J , Sana H , Taylor W D
Published: November 2023

A sub-set of the 67 Be-type stars observed in 30 Doradus during the VLT-FLAMES Tarantula Survey (VFTS) campaign have been analysed to estimate atmospheric parameters and chemical compositions, in particular their nitrogen abundance. Reliable results were found for 23 targets comprising the largest Large Magellanic Cloud sample currently available. The nitrogen abundance estimates have been compared with predictions from evolutionary models for rapidly rotating single stars (or non-interacting multiple systems) and for interacting binaries. The observations appear to be incompatible with all the targets having a single star evolutionary history. The results agree better with a binary evolutionary history with at least 30 per cent of the VFTS sample having apparently evolved by this pathway. These conclusions are consistent with a previous analysis of the ve sin i-estimates for this Be-type sample.
Bulge–disc decomposition of the Hydra cluster galaxies in 12 bands
Authors: Lima-Dias Ciria , Monachesi Antonela , Torres-Flores Sergio , Cortesi Arianna , Hernández-Lang Daniel , P. Montaguth Gissel , Jiménez-Teja Yolanda , Panda Swayamtrupta , Menéndez-Delmestre Karín , Gonçalves Thiago S , Méndez-Hernández Hugo , Telles Eduardo , Dimauro Paola , Bom Clécio R , Mendes de Oliveira Claudia , Kanaan Antonio , Ribeiro Tiago , Schoenell William
Published: November 2023

When a galaxy falls into a cluster, its outermost parts are the most affected by the environment. In this paper, we are interested in studying the influence of a dense environment on different galaxy’s components to better understand how this affects the evolution of galaxies. We use, as laboratory for this study, the Hydra cluster which is close to virialization; yet it still shows evidence of substructures. We present a multiwavelength bulge–disc decomposition performed simultaneously in 12 bands from S-PLUS (Southern Photometric Local Universe Survey) data for 52 galaxies brighter than mr = 16. We model the galaxies with a Sérsic profile for the bulge and an exponential profile for the disc. We find that the smaller, more compact, and bulge-dominated galaxies tend to exhibit a redder colour at a fixed stellar mass. This suggests that the same mechanisms (ram-pressure and tidal stripping) that are causing the compaction in these galaxies are also causing them to stop forming stars. The bulge size is unrelated to the galaxy’s stellar mass, while the disc size increases with greater stellar mass, indicating the dominant role of the disc in the overall galaxy mass–size relation found. Furthermore, our analysis of the environment unveils that quenched galaxies are prevalent in regions likely associated with substructures. However, these areas also harbour a minority of star-forming galaxies, primarily resulting from galaxy interactions. Lastly, we find that ∼37 per cent of the galaxies exhibit bulges that are bluer than their discs, indicative of an outside-in quenching process in this type of dense environments.
Sensitivity and specificity of folate receptor α-positive circulating tumour cells in gastric cancer
Authors: Cao Beibei , Liu Liang , Zhang Rui , Dong Hongliang , Shen Jie
Published: November 2023

Purpose

We aimed to investigate whether folate receptor α (FRα)-positive circulating tumour cells (CTCs) could be used as a noninvasive liquid biopsy approach in gastric cancer (GC).

Methods

Tissue microarray and bioinformatic analyses were used to evaluate FRα expression in GC. Patients with FRα-positive CTC examinations at our institute between July 2021 and May 2022 were retrospectively evaluated. Receiver operating characteristic curves were used to evaluate the diagnostic performance of FRα-positive CTCs in GC.

Results

FRα was highly expressed and associated with poor prognosis in GC based on public database. Data for 163 patients (20 with benign disease and 143 with GC) were retrospectively collected. FRα-positive CTC levels were significantly higher in the GC group than in the benign disease group (12.15 ± 1.47 FU/3 ml vs. 10.47 ± 1.63 FU/3 ml, P < 0.01). FRα-positive CTC levels were also elevated in GC patients with vessel/neuron invasion or extra-nodal tumour deposits (12.31 ± 1.47 FU/3 ml vs. 11.77 ± 1.38 FU/3 ml, P = 0.037). Areas under the curve of FRα-positive CTC levels for GC and early GC were 0.774 (P < 0.001) and 0.736 (P = 0.005). With a cut-off value of 10.95 FU/3 ml, the Youden indexes for GC and early GC were 0.502 (sensitivity = 85.2% and specificity = 65.0%) and 0.450 (sensitivity = 80.0% and specificity = 65.0%), respectively.

Conclusion

FRα-positive CTC detection by noninvasive liquid biopsy is a useful and effective approach for screening of patients with GC.

Key messages

What is already known on this topic

Early detection is important in the treatment of gastric cancer. However, noninvasive diagnostic techniques with adequate sensitivity are lacking.

What this study adds

The diagnostic performance of folate receptor-positive circulating tumour cells was better than that of carcinoembryonic antigen. With the optimal cut-off values, the sensitivities of folate receptor-positive circulating tumour cells in the diagnosis of gastric cancer and early gastric cancer were 85.2% and 80.0%, respectively.

How this study might affect research, practice, or policy

Folate receptor-positive circulating tumour cell examination is a promising noninvasive approach for the screening of patients with gastric cancer.
Trends in research grant applications and outcomes among medical students in the United Kingdom: a national self-reported cross-sectional survey
Authors: Inyang Deborah , Madume Rachael , Corriero Anna Chiara , Sofela Agbolahan , Osunronbi Temidayo ,   REMED-UK collaborators
Published: November 2023

Background

Research funding disparities contribute to clinical academic workforce inequalities. Hence, our study explores the association between student demographics and research grant application rates and outcomes among UK medical students.

Methods

This is a national multicentre cross-sectional survey of UK medical students in the 2020–21 academic year. Multiple zero-inflated negative binomial regression and generalized linear model (binomial distribution; logit link) were utilized to investigate the association between student demographics, number of grant applications submitted, and successful grant applications (yes or no). P-values less than a Bonferroni-corrected significance level of 0.05/36 = 0.0014 were considered to be statistically significant.

Results

A total of 1528 students participated from 36 medical schools. One hundred fifty-one respondents (9.9%) had applied for research grants. Black students submitted applications 2.90 times more often than white students [Incident rate ratio (IRR): 2.90, 95% confidence interval (CI): 1.37–6.16], with no ethnic disparity in the odds of successful applications. Gender did not influence application rates significantly (P = .248), but women were 4.61 times more likely to secure a grant than men [odds ratio: 4.61, 95% CI: 2.04–10.4]. Being a PubMed-indexed author was associated with increased grant application submission rates [IRR: 3.61, 95% CI: 2.20– 5.92] while conducting more research was associated with greater odds of securing a grant [odds ratio: 1.42, 95% CI: 1.17– 1.73].

Conclusion

Although black students submitted more applications, ethnicity did not influence success rates. Gender did not influence application rates, but women were more successful. These findings underscore the need for strategies supporting women and underrepresented students for continued academic achievement after graduation.

Key Messages

What is already known on this topic Research funding for post-PhD researchers is believed to be a major driver of gender and ethnic inequalities in the clinical academic workforce.Students who receive research grants are more likely to receive postgraduate research grants.

What this study adds Black students applied for more research grants than white students, but there were no ethnic differences in the odds of securing a grant.There were no gender differences in the research grant application rates. However, female students had greater odds of securing research grants compared to male students.

How this study might affect research, practice or policy Medical schools should incorporate grant writing skills into the undergraduate research curriculum. Also, to sustain women’s academic success post medical school, the NIHR and affiliates should provide research award extensions and childcare support for women when required.
Neighborhood Income Mobility and Risk of Neonatal and Maternal Morbidity
Authors: Jairam Jennifer A. , Vigod Simone N. , Siddiqi Arjumand , Guan Jun , Boblitz Alexa , Wang Xuesong , O'Campo Patricia , Ray Joel G.
Published: November 2023

(Abstracted from JAMA Network Open 2023;6(5):e2315301)

Women of low socioeconomic position are more likely to have poorer pregnancy outcomes than those of higher socioeconomic position, according to a growing body of epidemiological studies. Residence in low socioeconomic areas is associated with limited availability, access, and quality of health and social services.
Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines: A Systematic Review and Meta-analysis
Authors: Gonzalez-Mantilla P. J. , Hu Y. , Myers S. M. , Finucane B. M. , Ledbetter D. H. , Martin C. L. , Moreno-De-Luca A.
Published: November 2023

(Abstracted from JAMA Pediatr 2023;177(5):472–478)

Exome sequencing (ES) is a powerful diagnostic tool that is now used routinely in diagnosing neurodevelopmental disorders, although it is not used as commonly as a tool for the diagnosis of cerebral palsy (CP). Cerebral palsy can and often does occur simultaneously with neurodevelopmental disorders such as intellectual disability (ID), autism spectrum disorder (ASD), and speech disorders, which are often evaluated by ES due to their significant genetic components and the variety of known genes that are associated with each disorder.
Adjuvant Human Papillomavirus Vaccination After Excisional Procedure for Cervical Intraepithelial Neoplasia, A Cost-effectiveness Analysis
Authors: Chaiken Sarina R. , Bruegl Amanda S. , Caughey Aaron B. , Emerson Jenna , Munro Elizabeth G.
Published: November 2023

(Abstracted from Obstet Gynecol 2023;141:756–763)

A precursor to one of the most common cancers in the world and the United States and worldwide (cervical malignancy) is cervical intraepithelial neoplasia (CIN). Because the causal agent is known to be human papillomavirus (HPV), a primary prevention method of HPV vaccination is universally recommended for individuals 9 to 26 years of age and is not universally recommended but is approved for individuals aged 27 to 45 years.
Endoscopic Sequential Decompression of Avascular Necrosis of the Femoral Head of Nontraumatic Origin: Description of a Surgical Technique
Authors: Aguilera-Bohórquez Bernardo , Sigüenza Cristina , Gerstner-Saucedo Jochen , Carvajal Álvaro
Published: November 2023

Introduction:

Treatment options for nontraumatic avascular necrosis of the femoral head (NAVNT) aim to reduce intraosseous pressure and restore vascular flow to prevent the collapse of the femoral head. The objective of this study was to describe a modification of the standard central decompression technique, called sequential decompression, in patients with NAVNT.

Materials and Methods:

Sequential decompression consists of 4 stages: (1) negative pressure release with capsulotomy, (2) bone decompression by removing the cortical from the anterior superior part of the femoral head-neck junction, (3) intramedullary decompression and stimulation of osteogenesis through tunnels from the anterolateral aspect of the femoral neck, and (4) stimulation of angiogenesis with the application of platelet-rich plasma in the subchondral plate.

Results:

Five cases (4 men and 1 woman, age: 28.8±16.4 y) were treated with the sequential decompression technique. A decrease in pain and an improvement in function were observed in all cases.

Conclusion:

We believe that the approach offered by sequential decompression impacts the different pathophysiological pathways of NAVNT, which helps control intraosseous pressure, removal of necrotic tissue, stimulation of angiogenesis, and bone regeneration.

Level of Evidence:

Level V, expert opinion.
Nonbronchoscopic Bronchoalveolar Lavage Improves Respiratory Culture Accuracy in Critically Ill Patients
Authors: Jeng Margaret , Orsini Erica M. , Yerke Jason , Mehkri Omar , Mireles-Cabodevila Eduardo , Khouli Hassan , Mujanovic Samin , Wang Xiaofeng , Duggal Abhijit , Vachharajani Vidula , Scheraga Rachel G.
Published: November 2023

OBJECTIVES:

Diagnosis of pneumonia is challenging in critically ill, intubated patients due to limited diagnostic modalities. Endotracheal aspirate (EA) cultures are standard of care in many ICUs; however, frequent EA contamination leads to unnecessary antibiotic use. Nonbronchoscopic bronchoalveolar lavage (NBBL) obtains sterile, alveolar cultures, avoiding contamination. However, paired NBBL and EA sampling in the setting of a lack of gold standard for airway culture is a novel approach to improve culture accuracy and limit antibiotic use in the critically ill patients.

DESIGN:

We designed a pilot study to test respiratory culture accuracy between EA and NBBL. Adult, intubated patients with suspected pneumonia received concurrent EA and NBBL cultures by registered respiratory therapists. Respiratory culture microbiology, cell counts, and antibiotic prescribing practices were examined.

SETTING:

We performed a prospective pilot study at the Cleveland Clinic Main Campus Medical ICU in Cleveland, Ohio for 22 months from May 2021 through March 2023.

PATIENTS OR SUBJECTS:

Three hundred forty mechanically ventilated patients with suspected pneumonia were screened. Two hundred fifty-seven patients were excluded for severe hypoxia (Fio
2 ≥ 80% or positive end-expiratory pressure ≥ 12 cm H2O), coagulopathy, platelets less than 50,000, hemodynamic instability as determined by the treating team, and COVID-19 infection to prevent aerosolization of the virus.

INTERVENTIONS:

All 83 eligible patients were enrolled and underwent concurrent EA and NBBL.

MEASUREMENTS AND MAIN RESULTS:

More EA cultures (42.17%) were positive than concurrent NBBL cultures (26.51%, p = 0.049), indicating EA contamination. The odds of EA contamination increased by eight-fold 24 hours after intubation. EA was also more likely to be contaminated with oral flora when compared with NBBL cultures. There was a trend toward decreased antibiotic use in patients with positive EA cultures if paired with a negative NBBL culture. Alveolar immune cell populations were recovered from NBBL samples, indicating successful alveolar sampling. There were no major complications from NBBL.

CONCLUSIONS:

NBBL is more accurate than EA for respiratory cultures in critically ill, intubated patients. NBBL provides a safe and effective technique to sample the alveolar space for both clinical and research purposes.
Single-cell dissection of the multicellular ecosystem and molecular features underlying microvascular invasion in HCC
Authors: Li Ke , Zhang Rui , Wen Fukai , Zhao Yunzheng , Meng Fanshuai , Li Qingyu , Hao Aimin , Yang Bailu , Lu Zhaoyang , Cui Yifeng , Zhou Meng
Published: November 2023

Background and Aims:

Microvascular invasion (MVI) is a crucial pathological hallmark of HCC that is closely associated with poor outcomes, early recurrence, and intrahepatic metastasis following surgical resection and transplantation. However, the intricate tumor microenvironment and transcriptional programs underlying MVI in HCC remain poorly understood.

Approach and Results:

We performed single-cell RNA sequencing of 46,789 individual cells from 10 samples of MVI+ (MVI present) and MVI- (MVI absent) patients with HCC. We conducted comprehensive and comparative analyses to characterize cellular and molecular features associated with MVI and validated key findings using external bulk, single-cell, and spatial transcriptomic datasets coupled with multiplex immunofluorescence assays. The comparison identified specific subtypes of immune and stromal cells critical to the formation of the immunosuppressive and pro-metastatic microenvironment in MVI+ tumors, including cycling T cells, lysosomal associated membrane protein 3+ dendritic cells, triggering receptor expressed on myeloid cells 2+ macrophages, myofibroblasts, and arterial i endothelial cells. MVI+ malignant cells are characterized by high proliferation rates, whereas MVI- malignant cells exhibit an inflammatory milieu. Additionally, we identified the midkine-dominated interaction between triggering receptor expressed on myeloid cells 2+ macrophages and malignant cells as a contributor to MVI formation and tumor progression. Notably, we unveiled a spatially co-located multicellular community exerting a dominant role in shaping the immunosuppressive microenvironment of MVI and correlating with unfavorable prognosis.

Conclusions:

This study provides a comprehensive single-cell atlas of MVI in HCC, shedding light on the complex multicellular ecosystem and molecular features associated with MVI. These findings deepen our understanding of the underlying mechanisms driving MVI and provide valuable insights for improving clinical diagnosis and developing more effective treatment strategies.
Evaluation of terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury using point-of-care echocardiography
Authors: Premkumar Madhumita , Kajal Kamal , Reddy K. Rajender , Izzy Manhal , Kulkarni Anand V. , Duseja Ajay Kumar , Sihag K. Bhupendra , Divyaveer Smita , Gupta Ankur , Taneja Sunil , De Arka , Verma Nipun , Rathi Sahaj , Bhujade Harish , Chaluvashetty Sreedhara B. , Roy Akash , Kumar Vishesh , Siddhartha Vuppada , Singh Virendra , Bahl Ajay
Published: November 2023

Background and Aims:

Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers.

Approach:

Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria.

Results:

One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9–4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p<0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8–4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2–12.2, p<0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine.

Conclusions:

CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI.
Spontaneous necrotizing soft-tissue infections in patient with diabetes: Case report
Authors: Sciano Donato , Mariano Francesco , Guida Giovanni , Marra Teresa , Carmine Pezzulo Massimo , Iarrobino Francesco , D’Ambrosio Alessandra , Andreano Mauro
Published: November 2023

Necrotizing skin and soft-tissue infections (NSTI) are rare but potentially life-threatening and disabling infections that often require intensive care unit admission. The initial presentation of a patient with NSTI can be misleading, as features of severe systemic toxicity can obscure sometimes less impressive skin findings. The infection can spread rapidly, and delayed surgery worsens the prognosis; hence, there is a limited role for additional imaging in critically ill patients. In addition, the utility of clinical scores is contested. Prompt surgery with aggressive debridement of necrotic tissue is required for source control and allows for microbiological sampling. Moreover, prompt administration of broad-spectrum antimicrobial therapy is warranted, with the addition of clindamycin for its effect on toxin production, both in empirical therapy and in targeted therapy for monomicrobial group A streptococcal and clostridial NSTI.
Microvasculature alterations of peripapillary retina and macula in systemic lupus erythematosus patients without ocular involvement by optical coherence tomography angiography
Authors: Li Huangdong , Yu ShuiLian , Li Peiyi , Zhang Jingyu , Maitiyaer Maierhaba , Huang Amy Michelle , Deng Qian , Yang Ruiming , Liang Jiamian , Huang Wenhui , Liu Zhiping
Published: November 2023

Purpose:

To evaluate microvasculature alterations of the peripapillary retina (PR) and macula and to assess if the changes can detect preclinical retinopathy in systemic lupus erythematosus (SLE) patients.

Methods:

Cross-sectional study of 32 SLE patients without retinopathy and 22 normal controls. Optical coherence tomography angiography was used to measure the microvasculature of the PR and macula. Vessel densities (VD, %) and fractal dimensions of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were calculated.

Results:

Compared to controls, macular VD of the whole image SCP (mVD of SCP-wi) and mVD of inferior SCP (mVD of SCP-i) were significantly reduced in SLE patients (p<0.05). The peripapillary VD (pVD) of a 2.5mm circle of SCP (pVD of SCPΦ2.5), pVD of SCPΦ3.5, and pVD of inferior region of the inner circle of SCP (pVD of SCP-ii) were significantly reduced in patients treated with hydroxychloroquine (HCQ) >5 years. mVD of SCP-wi declined with age (β=-0.12; p<0.01) and pVD of SCP-ii declined with hydroxychloroquine cumulative dose (β=-0.01; p<0.01). mVD of SCP-i had the best discrimination power of 0.77 (p<0.01).

Conclusion:

SLE patients without ocular involvement had microvasculature alterations that were particularly evident in the SCP. PR microvasculature may be reduced in patients with longer HCQ treatment.
Association of Diabetic Macular Edema with Quality of Life in Type 2 diabetes patients: The Fushun Diabetic Retinopathy Cohort Study
Authors: Zang Bo , Rong Shisong , Wang Yu , Feng Kemi , Ding Xiaoxia , Wen Liang , Zang Dongxiao , Li Dong , Liang Yuanbo , Wang Fenghua , Zhai Gang
Published: November 2023

Purpose:

To report the vision-related quality of life (VRQoL) in patients with diabetic macular edema (DME) in a population-based study.

Methods:

In this cross-sectional study, we analyzed 1659 subjects with type 2 diabetes. Questionnaires were administered to assess the patient’s VRQoL. DME severity was graded according to established protocols. A subject’s DME score ranged from 1 (no DME in either eye) to 7 (severe bilateral DME) using predefined criteria.

Results:

Composite NEI-VFQ-25 scores for participants with DME were 88.9 (interquartile range [IQR]: 76.2, 94.9), compared to 92.0 (IQR: 82.7, 96.0) for those without DME (P < 0.001). Locally weighted scatterplot smoothing (LOWESS) plots depicted a consistent decline in composite NEI-VFQ-25 scores corresponding to the escalation of bilateral DME severity: starting from 88.59 for no DME in either eye, progressing through 86.65, 85.83, 85.31, 84.91, 83.85, and culminating at 82.71 for bilateral severe DME. Notably, the LOWESS plots highlighted significant NEI-VFQ-25 composite score reduction at unilateral mild DME (slope m= -1.94).

Conclusion:

Significant changes in VRQoL manifest in the early stage of DME. Therefore, early identification and intervention for these patients are crucial clinical objectives.
Short-Term Efficacy and Safety of Phacoemulsification Associated With iStent Inject W in Patients With Controlled Open Angle Glaucoma
Authors: Louanchi Yanis , Brasnu Emmanuelle , Hamard Pascale , Aragno Vittoria , Baudouin Christophe , Labbé Antoine
Published: November 2023

Précis:

The iStent inject W implanted during phacoemulsification effectively reduces IOP.

Purpose:

The purpose of this study was to evaluate the efficacy and safety of iStent inject W combined with phacoemulsification in patients with controlled open angle glaucoma undergoing cataract surgery.

Patients and Methods:

We conducted a retrospective, bicentric study of patients with controlled chronic open angle glaucoma who underwent phacoemulsification combined with the injection of 2 iStent inject Ws. Patient characteristics, including intraocular pressure (IOP) and the number of glaucoma medications, were evaluated preoperatively and 1 week, 1 month, and 6 months postoperatively. The primary end point was IOP reduction, and the secondary end point was the reduction in the number of glaucoma medications.

Results:

In this study, 85 eyes were included. The majority of patients had primary open angle glaucoma (85% of eyes). Preoperative mean IOP was 16.1±2.0 mm Hg with a mean of 2.3±0.5 glaucoma medications. At 1 week postoperatively, the mean IOP was 16.7±3.1 mm Hg with a mean of 2.0±0.7 hypotensive medications. At 1 and 6 months, the mean IOP was 14.2±2.1 and 13.0±1.5 mm Hg, with a mean of 2.0±0.6 and 1.8±0.5 glaucoma medications, respectively. The percentage IOP reduction at 1 and 6 months was 11.6% (P=0.001) and 19.3% (P<0.0001), respectively. Regarding glaucoma medications, at 1 and 6 months, the reduction in the number of medications was 12.9% (P=0.025) and 22.4% (P=0.003), respectively. The most frequent significant postoperative adverse events were corneal edema in 7%, IOP spikes in 6%, and hyphema in 6% of eyes, which resolved spontaneously.

Conclusions:

The iStent inject W implanted during phacoemulsification effectively reduces IOP and the number of glaucoma medications needed at 6 months of follow-up, with a favorable safety profile in patients with controlled open angle glaucoma.
Predictors of Sun-Protective Behaviors and Sunburn in the United States Population
Authors: Ward Jeanne , Sha Shuying , Hardin-Fanning Frances
Published: November 2023

Skin cancer is the most diagnosed cancer in the United States. Despite years of education about prevention, incidence is increasing. There are mixed findings about sun protection factors' relationship to preventing sunburn. This study aimed to identify the factors associated with the performance of sun-protective behaviors and understand sunburn risk factors, which relate to skin cancer risk, controlling for demographic factors. This is a secondary analysis of cross-sectional data from the National Health and Nutrition Examination Survey from 2017 to 2018. Data were subset to U.S. participants ages 20 years and older who answered the dermatology questions, which included 3,404 people. A hierarchical logistic regression analysis was conducted in SPSS to investigate the contribution of several factors predicting sun-protective behaviors while controlling for demographic variables. In addition, multiple logistic regression analyses were used to examine potential factors related to getting a sunburn. Statistical significance was p < .05. Race, education, birth country, gender, and sun sensitivity were significant predictors of sun protection behaviors. Those who used sunscreen with a higher frequency and those with severe sun sensitivity had the highest odds of reporting a sunburn. Younger age and severe sun sensitivity were associated with multiple sunburns. The discrepancy between the perceived level of sun sensitivity and the incidence of sunburn suggests that people need to be adequately informed about the risks of sunburn. This finding supports the need for additional research to understand the attitudes and health beliefs toward sunburn and skin cancer prevention.
The potential role of social care in reducing childhood obesity
Authors: Cruz Herrera Evianna , Figueroa-Nieves Amanda I. , Woo Baidal Jennifer A.
Published: November 2023

Purpose of review

This review evaluates the current evidence for relationships of social factors with childhood obesity and for a role of social care in reduction of childhood obesity.

Recent findings

Most literature on the relationship between social factors and childhood obesity has examined food insecurity as a risk factor for obesity. Associations between food insecurity and excess weight in children are most consistent during infancy and among those with food insecurity at more than one time point. A few pilot food security interventions that link patients with produce or groceries show feasibility and potential promise for reducing childhood obesity risk factors. However, full-scale, randomized studies to examine interventions that reduce social needs and their effects on childhood obesity are lacking. Future research is needed to examine holistic social care approaches to effectively reduce childhood obesity risk factors.

Food insecurity acts as a barrier to childhood obesity prevention and treatment. Patient-centered, validated measures of social needs and effective interventions to address social needs are needed to equitably prevent and treat childhood obesity.
Long-term outcome of centrally located hepatocellular carcinoma treated by neoadjuvant radiotherapy and radical resection: a propensity score matched study
Authors: Tao Changcheng , Wu Fan , Liu Yue , Wang Liming , Wang Hongwei , Chen Bo , Rong Weiqi , Wu Jianxiong
Published: November 2023

Objective:

Centrally located hepatocellular carcinoma (HCC) typically presents challenges in surgical intervention and is associated with a bleak prognosis. In order to address this pressing issue, it is imperative to identify a comprehensive treatment approach, such as neoadjuvant radiotherapy (neoRT), that can enhance the prognosis of patients diagnosed with centrally located HCC.

Methods:

Patients who had surgical resections for HCC between March 2015 and December 2020 were included in the study. Patients were assigned to either the neoRT combined with liver resection (neoRT+LR) group or the liver resection alone (LR) group. The study employed propensity-score analysis and Cox proportional-hazards regression models as research methodologies. Using the Kaplan–Meier method, overall survival (OS) and disease-free survival (DFS) were estimated in patients.

Results:

During the study, 162 patients were enrolled, with 41 receiving neoRT+LR and 121 receiving LR. The duration of the median follow-up period was 45 months. The 1-year, 3-year, and 5-year OS rates were 95, 70, and 70% for patients in the neoRT+LR group, and 82, 64, and 54% for patients in the LR group, respectively. The 1-year, 3-year, 5-year DFS rates were 71, 53, and 37% for patients in the neoRT+LR group, and 52, 38, and 34% for patients in the LR group, respectively. A successful matching of 37 patients was achieved through propensity-score analysis. OS and DFS after matching analysis was statistically different between the two groups ( P=0.0099, P=0.034, respectively). neoRT was an independent prognostic factor for OS and DFS [hazard ratio (HR)=0.47, 95% CI: 0.24–0.93; HR=0.56, 95% CI: 0.34–0.92, respectively]. According to matching analysis, there were no statistically significant differences observed in terms of baseline characteristics, surgical safety, and complications between the groups.

Conclusion:

Liver resection and neoRT can be advantageous for patients with centrally located HCC.
Application of CRISPR/Cas9 in the management of Alzheimer’s disease and Parkinson’s disease: a review
Authors: Thapar Nandita , Eid Mosab Ahmad Fathi , Raj Nishchita , Kantas Theodosios , Billing Harbir S. , Sadhu Dhavalkumar
Published: November 2023

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) nucleases system (CRISPR/Cas9) is a popular gene-editing technology with an expanding scope in the field of medicine. Recent studies have investigated the role of CRISPR/Cas9 system in the treatment of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Since the risk of occurrence of both conditions is strongly associated with genetic mutations and variations, the use of gene-editing technologies to rectify these genetic errors becomes relevant. The CRISPR/Cas9 system has been tested in AD, which has led to a decrease in either amyloid beta deposition or tau phosphorylation in cells. Likewise, genetic mutations in cells affected by PD have been corrected with promising results in initial studies undertaken. Therefore, the use of the CRISPR/Cas9 system should be expanded among different populations to understand its efficacy and safety in depth among neurodegenerative conditions.