bluuebunny/crossref_metadata_2025 huggingface dataset:
The Chrysanthemum Phenotype of Idiopathic Multifocal Choroiditis
Authors: Ramtohul Prithvi , Cicinelli Maria Vittoria , Dolz-Marco Rosa , Gal-Or Orly , Mrejen Sarah , García-Martínez Jesús R , Goldberg Alla , Cunha de Souza Eduardo , Miserocchi Elisabetta , Cunningham Emmett T. , Yannuzzi Lawrence A. , Freund K. Bailey , Tsui Edmund
Published: April 2023

Purpose:

To describe the clinical characteristics and multimodal imaging (MMI) features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as “chrysanthemum lesions”.

Methods:

Retrospective, observational, multi-center case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented.

Results:

Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8±17.0 years (range, 7 – 78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far-periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography (OCT), chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch’s membrane (RPE/BrM). Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on OCT-angiography.

Conclusion:

Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the high number of lesions, and the high prevalence of exclusive mid- and far-peripheral involvement may represent a distinctive phenotype of iMFC.
The evolution of refractive surgery training
Authors: Arboleda Nathan , Yi Joseph , Kang Joann J.
Published: April 2023

Purpose of review

Although refractive surgery is one of the most commonly performed ophthalmic procedures, there is a relative paucity of literature on residency and fellowship refractive surgery education. The purpose of this article is to review the current state and recent updates to refractive surgery education and to evaluate the safety and visual outcomes of trainee performed refractive procedures.

Recent findings

Currently, there is no standard refractive surgery curriculum in the United States apart from required mandatory minimum refractive requirements for residents and fellows. Our survey of residency programs confirms that refractive training is extremely varied, ranging from a dedicated refractive rotation with direct surgical experience to only didactics or observation of procedures. There is a proposed standardized framework for refractive surgery training for the military, which may be a starting point in developing a more comprehensive refractive surgery curriculum in residency education. Multiple studies have reinforced the safety of resident and fellow performed refractive surgery.

Refractive surgery is an increasingly popular procedure and a more comprehensive refractive education is paramount. Future studies are needed to determine how best to provide the fundamental training and surgical experience for trainees in the fast-changing landscape of refractive surgery.
Research Progress of the Association of the Neutrophil Elastase with Sepsis-related Acute Lung Injury
Authors: Qiu Chuiyan , Zheng Xinglong , Qu Zhongkai , Zhang Luming , Hu Hai , Lu Xuehao , Yin Haiyan
Published: April 2023

Sepsis is considered a life-threatening organ dysfunction resulting from a dysregulation of the body's response to the infection, a syndrome of physiological, pathological, and biochemical abnormalities caused by infection. The prevention and treatment of sepsis-related acute lung injury has become a hot spot in sepsis research in recent years. Neutrophil elastase (NE) is a multifunctional serine protease released by neutrophils cells, which can participate in the regulation of the inflammatory response in the body and directly affect the occurrence and development of inflammation. This article reviews the pathogenesis of sepsis-related lung injury and the mechanism of action, clinical application and prospect of neutrophil elastase inhibitor (NEI).
An interprofessional clinical experience to address social determinants of health
Authors: Hickey Mary T. , Stillo Marco , Marquez Crystal
Published: April 2023

The importance of effective interprofessional communication and collaboration as a strategy to improve patient outcomes has been documented in the literature. Efforts to integrate interprofessional education have been difficult to actualize due to myriad factors in academic and clinical settings. The COVID public health emergency presented an unexpected opportunity to address the needs of an underserved community through an interprofessional clinical experience between medical and APRN students. A screening tool and resource-driven algorithm were developed and launched by students in the college of medicine, for the patients of a university hospital clinic. This initiative helped meet the needs of the community, with the value-added benefit of an interprofessional clinical experience. Using a train-the-trainer model, students were oriented to the project and an online platform for real-time collaboration. Results of this initiative were positive. Approximately 100 medical and APRN students participated and contacted 1,489 patients in the community. Medical and social needs were addressed for 681 patients, and urgent social needs were addressed for 30 people. Students gained valuable clinical experience and had opportunities to identify and address social determinants of health while collaborating with medical student counterparts.
Reporting Standards for Diagnostic Testing
Authors: Ost David E. , Feller-Kopman David J. , Gonzalez Anne V. , Grosu Horiana B. , Herth Felix , Mazzone Peter , Park John E.S. , Porcel José M. , Shojaee Samira , Tsiligianni Ioana , Vachani Anil , Bernstein Jonathan , Branson Richard , Flume Patrick A. , Akdis Cezmi A. , Kolb Martin , Portela Esther Barreiro , Smyth Alan
Published: April 2023

Diagnostic testing is fundamental to medicine. However, studies of diagnostic testing in respiratory medicine vary significantly in terms of their methodology, definitions, and reporting of results. This has led to often conflicting or ambiguous results. To address this issue, a group of 20 respiratory journal editors worked to develop reporting standards for studies of diagnostic testing based on a rigorous methodology to guide authors, peer reviewers, and researchers when conducting studies of diagnostic testing in respiratory medicine. Four key areas are covered, including defining the reference standard of truth, measures of dichotomous test performance when used for dichotomous outcomes, measures of multichotomous test performance for dichotomous outcomes, and what constitutes a useful definition of diagnostic yield. The importance of using contingency tables for reporting results is addressed with examples from the literature. A practical checklist is provided as well for reporting studies of diagnostic testing.
Blood pressure surge with alarm is reduced after exercise and diet intervention in firefighters
Authors: Feairheller Deborah L , Smith Macie , Carty Megan , Reeve Emily H
Published: April 2023

Background

Cardiac-related incidents are a public health concern for tactical occupations, and cardiovascular disease rates are higher in these populations compared with civilians. Research is needed to examine blood pressure (BP) responses in firefighters. The pager alert is one occupational hazard, and it is unknown if lifestyle change can reduce the systolic surge response.

Purpose

To measure BP surge with alarm in firefighters to determine whether the magnitude is lower after a 6-week tactical exercise and Mediterranean-diet intervention.

Methods

Systolic BP (SBP) and diastolic BP (DBP) surge levels, circulating markers, vascular health, and fitness were analyzed. BP surge with alarm was captured during a 12-hour workshift. Exercise and diet were self-reported. Diet was tracked with diet scores based on number of servings.

Results

A total of 25 firefighters (43.4 ± 13.9 years) participated. We found changes in the magnitude of BP surge with alarm (SBP surge from16.7 ± 12.9 to 10.5 ± 11.7 mmHg, P < 0.05; DBP surge from 8.2 ± 10.8 to 4.9 ± 5.6 mmHg, P > 0.05) after intervention. We confirm that clinical (127.6 ± 9.1 to 120 ± 8.2 mmHg) and central (122.7 ± 11.3 to 118.2 ± 10.7 mmHg) SBP levels improve with exercise and diet. We report for the first time in firefighters that oxidative stress markers superoxide dismutase (9.1 ± 1.5 to 11.2 ± 2.2 U/ml) and nitric oxide (40.4 ± 7 to 48.9 ± 16.9 μmol/l) levels improve with an exercise and diet intervention.

Conclusion

These findings have implications toward the benefit that short-term lifestyle changes make toward reducing the alarm stress response in first responders.
Renal effects of cullin 3 mutations causing familial hyperkalemic hypertension
Authors: Cornelius Ryan J. , Maeoka Yujiro , McCormick James A.
Published: April 2023

Purpose of review

Mutations in the E3 ubiquitin ligase scaffold cullin 3 (CUL3) cause the disease familial hyperkalemic hypertension (FHHt) by hyperactivating the NaCl cotransporter (NCC). The effects of these mutations are complex and still being unraveled. This review discusses recent findings revealing the molecular mechanisms underlying the effects of CUL3 mutations in the kidney.

Recent findings

The naturally occurring mutations that cause deletion of exon 9 (CUL3-Δ9) from CUL3 generate an abnormal CUL3 protein. CUL3-Δ9 displays increased interaction with multiple ubiquitin ligase substrate adaptors. However, in-vivo data show that the major mechanism for disease pathogenesis is that CUL3-Δ9 promotes degradation of itself and KLHL3, the specific substrate adaptor for an NCC-activating kinase. CUL3-Δ9 displays dysregulation via impaired binding to the CSN and CAND1, which cause hyperneddylation and compromised adaptor exchange, respectively. A recently discovered CUL3 mutant (CUL3-Δ474–477) displays many similarities to CUL3-Δ9 mutations but some key differences that likely account for the milder FHHt phenotype it elicits. Furthermore, recent work suggests that CUL3 mutations could have unidentified complications in patients and/or a predisposition to renal injury.

This review summarizes recent studies highlighting advances in our understanding of the renal mechanisms by which CUL3 mutations modulate blood pressure in FHHt.
Clinical Outcomes of an Intensity Program for Children With Movement Challenges
Authors: Schreiber Joseph , Wenskovitch John , Belt Janice , O'Donnell Amy , Wolf Debra
Published: April 2023

Purpose:

Physical therapists at an outpatient pediatric facility developed and implemented an Intensity Program for children with movement challenges. The program was initiated on the basis of best evidence, parent advocacy, and clinician expertise. The purpose of this investigation is to analyze outcome data gathered from the program since 2012 to determine the effect of the program along with any specific child characteristics that were more likely to lead to positive outcomes.

Methods:

A variety of outcome data were analyzed to compare preprogram performance with postprogram performance.

Results:

Program participants made statistically significant and clinically important improvement in most outcome measures. Parents were highly satisfied with the program, including 98% of respondents who indicated that they would like to repeat their participation in the program.

Conclusions:

The results of this investigation suggest that many children with movement challenges are likely to benefit from participation in an Intensity Program.
Intersectionality-informed analysis of durable viral suppression disparities in people with HIV
Authors: Rivera Adovich S. , Rusie Laura K. , Feinstein Matthew J. , Siddique Juned , Lloyd-Jones Donald M. , Beach Lauren B.
Published: April 2023

Objective:

The aim of this study was to examine drivers of durable viral suppression (DVS) disparities among people with HIV (PWH) using quantitative intersectional approaches.

Design:

A retrospective cohort analysis from electronic health records informed by intersectionality to better capture the concept of interlocking and interacting systems of oppression.

Methods:

We analyzed data of PWH seen at a LGBTQ federally qualified health center in Chicago (2012–2019) with at least three viral loads. We identified PWH who achieved DVS using latent trajectory analysis and examined disparities using three intersectional approaches: Adding interactions, latent class analysis (LCA), and qualitative comparative analysis (QCA). Findings were compared with main effects only regression.

Results:

Among 5967 PWH, 90% showed viral trajectories consistent with DVS. Main effects regression showed that substance use [odds ratio (OR) 0.56, 0.46–0.68] and socioeconomic status like being unhoused (OR: 0.39, 0.29–0.53), but not sexual orientation or gender identity (SOGI) were associated with DVS. Adding interactions, we found that race and ethnicity modified the association between insurance and DVS (P for interaction <0.05). With LCA, we uncovered four social position categories influenced by SOGI with varying rates of DVS. For example, the transgender women-majority class had worse DVS rates versus the class of mostly nonpoor white cisgender gay men (82 vs. 95%). QCA showed that combinations, rather than single factors alone, were important for achieving DVS. Combinations vary with marginalized populations (e.g. black gay/lesbian transgender women) having distinct sufficient combinations compared with historically privileged groups (e.g. white cisgender gay men).

Conclusion:

Social factors likely interact to produce DVS disparities. Intersectionality-informed analysis uncover nuance that can inform solutions.
Mortality in hepatitis C virus-cured vs. hepatitis C virus-uninfected people with HIV
Authors: Requena Maria-Bernarda , Grabar Sophie , Lanoy Emilie , Pialoux Gilles , Billaud Eric , Duvivier Claudine , Merle Philippe , Piroth Lionel , Tattevin Pierre , Salmon Dominique , Weiss Laurence , Costagliola Dominique , Lacombe Karine
Published: April 2023

Objective:

It is unknown whether hepatitis C virus (HCV)-cured people with HIV (PWH) without cirrhosis reached the same mortality risk as HCV-uninfected PWH. We aimed to compare mortality in PWH cured of HCV by direct-acting antivirals (DAAs) to mortality in individuals with HIV monoinfection.

Design:

Nationwide hospital cohort.

Methods:

HIV-controlled participants without cirrhosis and HCV-cured by DAAs started between September 2013 and September 2020, were matched on age (±5 years), sex, HIV transmission group, AIDS status, and body mass index (BMI) (±1 kg/m2) to up to 10 participants with a virally suppressed HIV monoinfection followed at the time of HCV cure ±6 months. Poisson regression models with robust variance estimates were used to compare mortality in both groups after adjusting for confounders.

Results:

The analysis included 3961 HCV-cured PWH (G1) and 33 872 HCV-uninfected PWH (G2). Median follow-up was 3.7 years in G1 [interquartile range (IQR): 2.0–4.6], and 3.3 years (IQR: 1.7–4.4) in G2. Median age was 52.0 years (IQR: 47.0–56.0), and 29 116 (77.0%) were men. There were 150 deaths in G1 [adjusted incidence rate (aIR): 12.2/1000 person-years] and 509 (aIR: 6.3/1000 person-years) in G2, with an incidence rate ratio (IRR): 1.9 [95% confidence interval (CI), 1.4–2.7]. The risk remained elevated 12 months post HCV cure (IRR: 2.4 [95% CI, 1.6–3.5]). Non-AIDS/non-liver-related malignancy was the most common cause of death in G1 (28 deaths).

Conclusions:

Despite HCV cure and HIV viral suppression, after controlling on factors related to mortality, DAA-cured PWH without cirrhosis remain at higher risk of all-cause mortality than people with HIV monoinfection. A better understanding of the determinants of mortality is needed in this population.
Altered methionine-sulfone levels are associated with impaired growth in HEU-children
Authors: Zhang Zhengzheng , Duri Kerina , Duisters Kevin L.W. , Schoeman Johannes C. , Chandiwana Panashe , Lindenburg Peter , Jaeger Julia , Ziegler Susanne , Altfeld Marcus , Kohler Isabelle , Harms Amy , Gumbo Felicity Z. , Hankemeier Thomas , Bunders Madeleine J.
Published: April 2023

Objective:

To determine immune-metabolic dysregulation in children born to women living with HIV.

Methods:

Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women living with HIV (WLHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.

Results:

Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signaling lipids) and 24 immune mediators (e.g. cytokines) were quantified. cART exposure was categorized as cART initiation preconception (long), cART initiation post-conception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HEU-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.

Conclusion:

These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WLHIV is associated with restricted infant growth.
Pharmacokinetics and pharmacodynamics of adult dolutegravir tablets in treatment-experienced children with HIV weighing at least 20 kg
Authors: Martyn-Dickens Charles , Ojewale Oluwayemisi , Sly-Moore Eugenia , Dompreh Albert , Enimil Anthony , Amissah Aikins Kofi , Bosomtwe Dennis , Appiah Augustina Frimpong , Sarfo Ama D. , Opoku Theresah , Asiedu Priscilla , Dong Stephen K. , Kusi-Amponsah Isaac , Maranchick Nicole , Peloquin Charles A. , Antwi Sampson , Kwara Awewura
Published: April 2023

Objective:

Limited pharmacokinetic/pharmacodynamic data are a barrier to the well tolerated scale-up of dolutegravir-based antiretroviral therapy (ART) in children. We examined the pharmacokinetic/pharmacodynamic of the adult film-coated dolutegravir 50 mg tablets in children with HIV infection weighing at least 20 kg.

Design:

A prospective, observational, pharmacokinetic, and safety study.

Methods:

Treatment-experienced children with HIV weighing at least 20 kg and evidence of viral load suppression on ART were enrolled and switched to dolutegravir-based therapy. After at least 4 weeks and 7 months on dolutegravir-based therapy, blood samples were collected at 0, 1, 4, 8, 12, and 24-h postdose. Dolutegravir concentrations were measured using validated LCMS/MS and pharmacokinetic parameters calculated by noncompartmental analysis. Descriptive statistics were used to summarize pharmacokinetic parameters and comparisons with published reference values.

Results:

Of 25 participants, 92% were on efavirenz-based ART and 60.0% were men. Dolutegravir mean exposure, peak and trough concentrations at both pharmacokinetic visits were higher than the mean reference values in adults and children weighing 20 kg to less than 40 kg treated with 50 mg once daily, but were closer to the mean values in adults given 50 mg twice a day. Children weighing 20 kg to less than 40 kg had even higher dolutegravir exposures. The regimens were well tolerated with good virologic efficacy through week 48.

Conclusion:

The higher dolutegravir exposure in our study population suggests that further studies and close monitoring should investigate the adverse effects of dolutegravir in more children and in the long term.
Racial, gender, and psychosocial disparities in viral suppression trends among people receiving coordinated HIV care in Los Angeles County
Authors: Li Michael J. , Chau Brendon , Garland Wendy H. , Oksuzyan Sona , Weiss Robert E. , Takada Sae , Kao Uyen , Lee Sung-Jae , Shoptaw Steven J.
Published: April 2023

Objective:

To longitudinally evaluate differences in HIV viral suppression (< 200 c/mL) by intersections of race/ethnicity, gender, and psychosocial issues in people with HIV in the Los Angeles County Medical Care Coordination Program.

Design:

We analyzed 187,830 viral load measurements over 10,184 people with HIV enrolled in the Medical Care Coordination Program between January 1, 2013 and March 1, 2020.

Methods: We fit Bayesian logistic hierarchical random effects models to test interactions between gender, race/ethnicity, and a psychosocial acuity score on viral suppression over time from 1 year prior to program enrollment to 24 months after enrollment.

Results:

The probability of viral suppression declined prior to enrollment, then increased and stabilized by 6 months after enrollment. Black/African American patients with low and moderate psychosocial acuity scores did not achieve the same increase in percentage of viral suppression as those in other racial/ethnic groups. Transgender women with high psychosocial acuity scores took longer (about 1 year) to achieve the same percentage of viral suppression as clients of other gender identities.

Conclusions:

Some racial/ethnic and gender disparities in viral suppression persisted after enrollment in the Los Angeles County Medical Care Coordination Program while accounting for psychosocial acuity score, which may be explained by factors not assessed in the program.
N-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis
Authors: Jia Degong , Guo Shanshan , Jia Zhixing , Gao Zhengjie , You Kun , Gong Jianping , Li Shengwei
Published: April 2023

Background.

N-acetylcysteine (NAC) is a potentially effective drug for treating ischemia–reperfusion injury in transplanted livers, but its effect remains controversial.

Methods.

A systematic review and meta-analysis of relevant clinical trials published and registered in the Cochrane Library, MEDLINE, EMBASE, ClinicalTrial.gov, WHO ICTRP, etc, before March 20, 2022 were conducted and registered with PROSPERO (CRD42022315996). Data were pooled using a random effects model or a fixed effects model based on the amount of heterogeneity.

Results.

Thirteen studies with 1121 participants, 550 of whom received NAC, were included. Compared with the control, NAC significantly reduced the incidence of primary graft nonfunction (relative risk [RR], 0.27; 95% confidence interval [CI], 0.08-0.96), the incidence of postoperative complications (RR, 0.52; 95% CI, 0.41-0.67), the peak postoperative aspartate transferase level (mean difference [MD], −267.52; 95% CI, −345.35 to −189.68), and the peak alanine transferase level (MD, −293.29; 95% CI, −370.39 to −216.20). NAC also improved 2-y (RR, 1.18; 95% CI, 1.01-1.38) graft survival rate. However, NAC increased the intraoperative cryoprecipitate (MD, 0.94; 95% CI, 0.42-1.46) and red blood cell (MD, 0.67; 95% CI, 0.15-1.19) requirements. Moreover, NAC was administered in various modes in these studies, including to the donor, recipient, or both. Subgroup analysis and network meta-analysis showed that NAC administration to recipients could play a more significant role than the other 2 administration modes.

Conclusions.

Our study supports the protective effect of NAC against LT-induced ischemia–reperfusion injury and shows better clinical outcomes of NAC administration to recipients.
Donor Liver Blood Tests and Liver Transplant Outcomes: UK Registry Cohort Study
Authors: Tingle Samuel J. , Bramley Rebecca , Goodfellow Michael , Thompson Emily R. , McPherson Stuart , White Steve A. , Wilson Colin H.
Published: April 2023

Background.

Safely increasing organ utilization is a global priority. Donor serum transaminase levels are often used to decline livers, despite minimal evidence to support such decisions. This study aimed to investigate the impact of donor “liver blood tests” on transplant outcomes.

Methods.

This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016–2019); adjusted regressions models were used to assess the effect of donor “liver blood tests” on outcomes.

Results.

A total of 3299 adult liver transplant recipients were included (2530 following brain stem death, 769 following circulatory death). Peak alanine transaminase (ALT) ranged from 6 to 5927 U/L (median = 45). Donor cause of death significantly predicted donor ALT; 4.2-fold increase in peak ALT with hypoxic brain injury versus intracranial hemorrhage (adjusted P < 0.001). On multivariable analysis, adjusting for a wide range of factors, transaminase level (ALT or aspartate aminotransferase) failed to predict graft survival, primary nonfunction, 90-d graft loss, or mortality. This held true in all examined subgroups, that is, steatotic grafts, donation following circulatory death, hypoxic brain injury donors, and donors, in which ALT was still rising at the time of retrieval. Even grafts from donors with extremely deranged ALT (>1000 U/L) displayed excellent posttransplant outcomes. In contrast, donor peak alkaline phosphatase was a significant predictor of graft loss (adjusted hazard ratio = 1.808; 1.016-3.216; P = 0.044).

Conclusions.

Donor transaminases do not predict posttransplant outcomes. When other factors are favorable, livers from donors with raised transaminases can be accepted and transplanted with confidence. Such knowledge should improve organ utilization decision-making and prevent future unnecessary organ discard. This provides a safe, simple, and immediate option to expand the donor pool.
Time to Whole Blood Transfusion in Hemorrhaging Civilian Trauma Patients: There Is Always Room for Improvement
Authors: Hosseinpour Hamidreza , Magnotti Louis J , Bhogadi Sai Krishna , Anand Tanya , El-Qawaqzeh Khaled , Ditillo Michael , Colosimo Christina , Spencer Audrey , Nelson Adam , Joseph Bellal
Published: April 2023

BACKGROUND:

Whole blood (WB) is becoming the preferred product for the resuscitation of hemorrhaging trauma patients. However, there is a lack of data on the optimum timing of receiving WB. We aimed to assess the effect of time to WB transfusion on the outcomes of trauma patients.

STUDY DESIGN:

The American College of Surgeons TQIP 2017 to 2019 database was analyzed. Adult trauma patients who received at least 1 unit of WB within the first 2 hours of admission were included. Patients were stratified by time to first unit of WB transfusion (first 30 minutes, second 30 minutes, and second hour). Primary outcomes were 24-hour and in-hospital mortality, adjusting for potential confounders.

RESULTS:

A total of 1,952 patients were identified. Mean age and systolic blood pressure were 42 ± 18 years and 101 ± 35 mmHg, respectively. Median Injury Severity Score was 17 [10 to 26], and all groups had comparable injury severities (p = 0.27). Overall, 24-hour and in-hospital mortality rates were 14% and 19%, respectively. Transfusion of WB after 30 minutes was progressively associated with increased adjusted odds of 24-hour mortality (second 30 minutes: adjusted odds ratio [aOR] 2.07, p=0.015; second hour: aOR 2.39, p=0.010) and in-hospital mortality (second 30 minutes: aOR 1.79, p=0.025; second hour: aOR 1.98, p=0.018). On subanalysis of patients with an admission shock index >1, every 30-minute delay in WB transfusion was associated with higher odds of 24-hour (aOR 1.23, p = 0.019) and in-hospital (aOR 1.18, p = 0.033) mortality.

CONCLUSIONS:

Every minute delay in WB transfusion is associated with a 2% increase in odds of 24-hour and in-hospital mortality among hemorrhaging trauma patients. WB should be readily available and easily accessible in the trauma bay for the early resuscitation of hemorrhaging patients.
Govind Swarup. 23 March 1929—7 September 2020
Authors: Kembhavi Ajit K. , Chengalur Jayaram N.
Published: April 2023

Professor Govind Swarup was a distinguished radio astronomer who drove the development of the field in India. Over a long career he built the Ooty Radio Telescope (ORT) and the Giant Metrewave Radio Telescope (GMRT), which are world-class facilities. Swarup was born in North India, had his undergraduate and post-graduate education at the University of Allahabad and then joined the National Physical Laboratory at New Delhi. He then travelled on a fellowship to Australia, to work on radio astronomy under J. L. Pawsey (FRS 1954). Later, in the USA, he completed his PhD with Ronald N. Bracewell at Stanford. Govind then accepted an offer made by Homi Bhabha FRS to begin radio astronomy work at the Tata Institute of Fundamental Research (TFIR). At TIFR, Govind conceived and built a novel, low cost, equatorially mounted cylindrical radio telescope, the ORT. The ORT was a versatile instrument and fuelled the growth of radio astronomy in India. In the late 1980s he conceived and led the construction of the GMRT, which again was based on a pioneering design. The GMRT is a remarkably successful instrument used by radio astronomers across the world. Govind Swarup has left behind a large group of radio astronomers who have continued his work and are finding new directions.
Feasibility of urban bird occurrence and nest amount evaluation by the street-view image virtual survey
Authors: Tian Panli , Wang Lei , Li Qi , Liang Chentao , She Danqi , Liu Siyu , Chen Yuwen , Yao Liuyang , Wang Weiqi , Wang Huimei , Wang Wenjie
Published: April 2023

Bird observation mainly relies on field surveys, which are time-consuming and laborious. In this study, we explored using street-view images in the virtual survey of urban birds and nests. Using the coastal city of Qingdao as the study area, 47 201 seamless spherical photos at 2741 sites were collected using the Baidu street-view (BSV) map. Single-rater-all photo checks and seven-rater-metapopulation checks were used to find inter–rater repeatability, the best viewing layer for BSV collection, and possible environments affecting the results. We also collected community science data for comparison. The BSV time machine was used to assess the temporal dynamics. Kappa square test, generalized linear model, redundancy ordination and ArcMap were used in the analysis. Different rater repeatability was 79.1% in nest evaluations and 46.9% in bird occurrence. A re-check of the different-rating photos can increase them to 92% and 70%. Seven-rater statistics showed that more than 5% sampling ratio could produce a non-significant different bird and nest percentage of the whole data, and the higher sampling ratio could reduce the variation. The middle-viewing layer survey alone could produce 93% precision of the nest checks by saving 2/3 of the time used; in birds, selecting middle and upper-view photos could find 97% of bird occurrences. In the spatial distribution, the nest's hotspot areas from this method were much greater than the community science bird-watching sites. The BSV time machine made it possible to re-check nests in the same sites but challenging the re-check of bird occurrences. The nests and birds can be observed more in the leafless season, on wide, traffic-dense coastal streets with complex vertical structures of trees, and in the gaps of tall buildings dominated by road forests. Our results indicate that BSV photos could be used to virtually evaluate bird occurrence and nests from their numbers, spatial distribution and temporal dynamics. This method provides a pre-experimental and informative supplement to large-scale bird occurrence and nest abundance surveys in urban environments.
Changing Epidemiology of Haemophilus influenzae carriage among Children in Lombok Island, Indonesia
Authors: Putri Nina Dwi , Salsabila Korrie , Prayitno Ari , Aprianti Shindy Claudya , Paramaiswari Wisiva Tofriska , Krisna Made Ananda , Safari Dodi
Published: April 2023

The Haemophilus influenzae serotype b (Hib) conjugate vaccine routine immunization program has been implemented for almost a decade, but there is a limited surveillance of H. influenzae carriage in Indonesia. H. influenzae was isolated from nasopharyngeal swab specimens from healthy children in Lombok Island, West Nusa Tenggara, Indonesia in 2018-2019. Serotyping was performed using quantitative polymerase chain reaction. Among 96 young children in Lombok Island, we identified H. influenzae from 40 out of 96 NP swab specimens (41.6%). We found 39 non-typeable H. influenzae (NTHi) and 1 serotype b isolate.
Ultra-Rare Genetic Variation in Relapsing Polychondritis: A Whole-Exome Sequencing Study
Authors: Luo Yiming , Ferrada Marcela A. , Sikora Keith A. , Rankin Cameron , Alessi Hugh , Kastner Daniel L. , Deng Zuoming , Zhang Mengqi , Merkel Peter A. , Kraus Virginia B. , Allen Andrew S. , Grayson Peter C.
Published: April 2023

Objective

Relapsing polychondritis (RP) is a systemic inflammatory disease of unknown etiology. The study objective was to examine the contribution of rare genetic variations in RP.

Methods

We performed a case-control exome-wide rare variant association analysis including 66 unrelated European American RP cases and 2923 healthy controls. Gene-level collapsing analysis was performed using Firth’s logistics regression. Pathway analysis was performed on an exploratory basis with three different methods: Gene Set Enrichment Analysis (GSEA), sequence kernel association test (SKAT) and higher criticism test. Plasma DCBLD2 levels were measured in patients with RP and healthy controls using enzyme-linked immunosorbent assay (ELISA).

Results

In the collapsing analysis, RP was associated with higher burden of ultra-rare damaging variants in theDCBLD2gene (7.6% vs 0.1%, unadjusted odds ratio = 79.8, p = 2.93 x 10-7). Patients with RP and ultra-rare damaging variants inDCBLD2had a higher prevalence of cardiovascular manifestations. Plasma DCBLD2 protein levels were significantly higher in RP than healthy controls (5.9 vs 2.3, p < 0.001). Pathway analysis showed statistically significant enrichment of genes in the tumor necrosis factor (TNF) signaling pathway driven by rare damaging variants inRELB,RELAandRELusing higher criticism test weighted by degree and eigenvector centrality.

Conclusions

This study identified specific rare variants inDCBLD2as putative genetic risk factors for RP. Genetic variation within the TNF pathway is also potentially associated with development of RP. These findings should be validated in additional patients with RP and supported by future functional experiments.
Clinical Performance of BD Veritor™ Assay Across SARS-CoV-2 Variants
Authors: Eckert Karen , Gutierrez Sebastian , Knight Brittany , Cooper Lauren
Published: April 2023

Background

Different rates of morbidity, mortality, transmission, and immune escape are associated with various strains of the SARS-CoV-2 virus. With the emergence of new strains during seasonal outbreaks, ensuring that antigen-based immunoassays can detect SARS-CoV-2 infections across identified circulating viral variants is a crucial component of infection control efforts.

Objective

To validate the performance of the BD Veritor System for Rapid Detection of SARS-CoV-2 Assay (BD Veritor assay) to detect SARS-CoV-2 across variants of concern (VOC) and variants of interest (VOI).

Methods

Using the Illumina NextSeq 2000 Sequencer, viral sequencing was performed on prospectively collected, then frozen, SARS-CoV-2 RT-PCR positive nasal swabs stored in universal transport media (UTM). Specimens from symptomatic and asymptomatic individuals were included in the study. Using the information obtained from the sequencing analysis, the performance of the BD Veritor System assay was evaluated against the highly sensitive molecular RT-PCR Quidel Lyra SARS-CoV-2 assay for each variant.

Results

The resulting PPA was 97.4% (95% CI: 86.8, 99.5) for detection of SARS-CoV-2 across all variants identified by Next Generation Sequencing (i.e., WHO-labeled variants Alpha, Delta, Gamma, Iota, Lambda, as well as two other non-labeled variants), with a 100% PPA for five of the six variant labels identified.

Conclusion

The results demonstrate the robust performance of the BD Veritor assay in detecting SARS-CoV-2 in clinical nasal specimens in selected variants. As new variants emerge, additional studies will be beneficial to ensure the sustained performance of SARS-CoV-2 assays.
scRNA-seq revealed the special IG H&L V(D)J allelic inclusion rearrangement and the high proportion dual BCR expressing B cells
Authors: Zhu Lanwei , Peng Qi , Wu Yingjie , Yao Xinsheng
Published: April 2023

abstract

Since the first report of V (D) J “ allelic exclusion/inclusion”and” dual BCR “in 1961, despite continuous new discoveries, the proportion and source mechanism of dual BCR under physiological conditions have been puzzling immuologists.This study takes advantage of the single cell V (D) J sequencing technology, which can perfectly match the heavy and light chains of BCR at the level of a single B cell, and obtain the full length mRNA sequence of the CDR3 region. By analyzing the pairing of functional IGH and IGL chains in single B cell from human and mouse bone marrow and peripheral blood, it was found that dual BCR B cells exhibit stable and high levels of expression.Among them, human bone marrow and peripheral blood contain about 10% dual (or multiple) BCR B cells, and mouse peripheral blood and bone marrow memory B cells contain about 20% dual (or multiple) BCR B cells. At the same time, we innovatively found that in each research sample of humans and mice, there are three (or more) functional rearrangements (mRNA level) of a single chain in a single B cell. By analyzing the position, direction and other compositional characteristics of the V(D)J gene family, we found that at least two(or more) of them are derived from over two(or more) specific allelic inclusion rearrangements of a single chromosome.(mRNA molecular level evidence).The results of this article provides new insights, new methods and modeling references for evaluating the proportion, molecular characteristics and source mechanisms of dual BCR B cells, as well as potential significance of allelic inclusion (exclusion escape) of V(D)J rearrangement.
Severe cirrhosis is associated with increased surgical mortality and morbidities in patients with hip fractures: a propensity-score matched analysis using a large inpatient database
Authors: Hamada Osamu , Shin Jung-ho , Tsutsumi Takahiko , Tsunemitsu Ayako , Sasaki Noriko , Kunisawa Susumu , Fushimi Kiyohide , Imanaka Yuichi
Published: April 2023

Objective

The aim of this study was to compare postoperative mortality and morbidities in patients with hip fractures undergoing surgery by Child-Pugh classes.

Summary Background Data

Advanced cirrhosis is associated with increased mortality in several types of surgery, but the impact of severity of cirrhosis on postoperative outcomes in patients with hip fractures remain unclear.

Methods

We analyzed data of patients with hip fracture within a large inpatient database. We performed three sets of 1:1 propensity-score matching for four groups: cases without cirrhosis, and Child-Pugh classes A, B and C. We compared in-hospital mortality, length of stay, hospitalization fee, rate of 30-day readmission and complications in the following three pairs: cases without cirrhosis vs Child-Pugh class A, Child-Pugh class A vs B, and Child-Pugh class B vs C.

Results

Among 833,648 eligible cases, propensity-score matching created 1,065 pairs between cases without cirrhosis vs Child-Pugh class A, 1,012 pairs between Child-Pugh class A vs B, and 489 pairs between Child-Pugh class B vs C. In-hospital mortality did not differ between cases with cirrhosis and those with Child-Pugh A classification (1.69% vs 1.41%; RD -0.28%; 95% CI: -1.34%–0.78%). In-hospital mortality was significantly higher in patients with Child-Pugh B classification than in those with A classification (1.48% vs 5.93%; RD 4.45%; 95% CI: 2.79%–6.10%), and in those with Child-Pugh C classification compared with those with B classification (6.34% vs 28.43%; RD 22.09%; 95% CI: 17.54%–26.63%). Among cases with cirrhosis, those in more severe Child-Pugh classes had longer length of stay, higher hospitalization fees and higher ratio of complications, such as acute liver failure, upper gastrointestinal bleeding and sepsis.

Conclusions

Our results could help to identify patients at high-risk of postoperative mortality and morbidity among those with both hip fracture and cirrhosis. Patients with Child-Pugh C classification may benefit from discussions about nonsurgical management, goals of care, and overall prognosis.

Mini-abstract

We conducted propensity-score matched analysis to examine mortality of groups of patients with hip fractures in a national patient database according to degree of severity of cirrhosis. Patients with higher Child-Pugh class of cirrhosis was shown to be associated with higher mortality.
Gemcitabine plus nab-paclitaxel preserves skeletal and cardiac mass and function in a murine model of pancreatic cancer cachexia
Authors: Narasimhan Ashok , Jengelley Daenique , Huot Joshua , Umberger Tara , Doud Emma , Mosley Amber L , Wang Meijing , Zhong Xiaoling , Counts Brittany , Rupert Joseph , Young Andrew , Bonetto Andrea , Horan Daniel , Robling Alexander G , Fishel Melissa , Kelley Mark , Koniaris Leonidas , Zimmers Teresa
Published: April 2023

More than 85% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer from cachexia, a debilitating syndrome characterized by the loss of muscle and fat and remains an unmet medical need. While chemotherapy remains an effective treatment option, it can also induce weight and muscle loss in patients with cancer. Gemcitabine combined with nab paclitaxel (GnP) is a first line treatment option for patients with PDAC but its effect on cachexia has not been comprehensively investigated. We interrogated the effects of GnP in a murine model of pancreatic cancer cachexia. Mice were orthotopically implanted with the cachexia inducing pancreatic cell line (KPC) and were administered GnP or vehicle. The controls underwent sham surgery. We defined GnP effects on cachexia and tumor burden by evaluating muscle and cardiac mass and function, fat mass, bone morphometry, and hematology measurements. We completed RNA sequencing and deep proteome profiling in skeletal and cardiac muscle. KPC+GnP reduced tumor burden over 50% and increased survival compared to KPC. KPC vehicle group had more than 15% muscle mass loss and decreased left ventricular mass, this was not present in KPC+GnP when compared to controls. RNA Seq and deep proteomics analyses suggested that muscle and cardiac dysfunction pathways activated in KPC group were either reversed or decreased in KPC+GnP. In all, our data suggests that GnP protects against muscle and cardiac wasting in an experimental model of PDAC cachexia.
Resource allocation strategies for insecticide-treated bed nets to achieve malaria eradication
Authors: Schmit Nora , Topazian Hillary M , Pianella Matteo , Charles Giovanni D , Winskill Peter , White Michael T , Hauck Katharina , Ghani Azra C
Published: April 2023

Background

Large reductions in the global malaria burden have been achieved in the last decades, but plateauing funding poses a challenge for progressing towards the ultimate goal of malaria eradication. We aimed to determine the optimal strategy to allocate global resources to achieve this goal.

Methods

Using previously published mathematical models ofPlasmodium falciparumandPlasmodium vivaxtransmission incorporating insecticide-treated nets (ITNs) as an illustrative intervention, we sought to identify the global funding allocation that maximized impact under defined objectives and across a range of global funding budgets.

Results

We found that the optimal strategy for case reduction closely mirrored an allocation framework that prioritizes funding for high-transmission settings, resulting in total case reductions of 76% (optimal strategy) and 66% (prioritizing high-transmission settings) at intermediate budget levels. Allocation strategies that had the greatest impact on case reductions were associated with lesser near-term impacts on the global population at risk, highlighting a trade-off between reducing burden and “shrinking the map” through a focus on near-elimination settings. The optimal funding distribution prioritized high ITN coverage in high-transmission settings endemic forP. falciparumonly, while maintaining lower levels in low-transmission settings. However, at high budgets, 62% of funding was targeted to low-transmission settings co-endemic forP. falciparumandP. vivax.

Conclusions

These results support current global strategies to prioritize funding to high-burdenP. falciparum-endemic settings in sub-Saharan Africa to minimize clinical malaria burden and progress towards elimination but highlight competing goals of reducing the global population at risk and addressing the burden ofP. vivax.
Amyloplast sedimentation repolarizes LAZYs to achieve gravity sensing in plants
Authors: Chen Jiayue , Yu Renbo , Li Na , Deng Zhaoguo , Zhang Xinxin , Zhao Yaran , Qu Chengfu , Yuan Yanfang , Pan Zhexian , Zhou Yangyang , Li Kunlun , Wang Jiajun , Chen Zhiren , Wang Xiaoyi , Wang Xiaolian , Dong Juan , Deng Xing Wang , Chen Haodong
Published: April 2023

Gravity controls directional growth of plants, and the classical starch-statolith hypothesis proposed more than a century ago postulates that amyloplast sedimentation in specialized cells initiates gravity sensing, but the molecular mechanism remains mysterious. Here, we report that gravistimulation by reorientation triggers the Mitogen-Activated Protein Kinase (MAPK) signaling-mediated phosphorylation of LAZY proteins, the key regulators of gravitropism accumulated more on the lower side of the plasma membrane in columella cells in regular growthArabidopsis. Phosphorylation of LAZY increases its interaction with several TOC proteins on the surface of amyloplasts, facilitating the translocation of LAZY proteins from the plasma membrane to the amyloplasts. Amyloplast sedimentation subsequently guides LAZY to relocate to the new lower side of the plasma membrane in columella cells, where LAZY induces asymmetrical auxin distribution and differential growth. Together, this study provides a molecular interpretation for the starch-statolith hypothesis: the organelle movement-triggered molecular polarity formation.