bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between the Severity of Adhesions and Desmoid Disease in Patients with Familial Adenomatous Polyposis: A Prospective Cohort Study
Authors: Faul Eleanor , Xhaja Xhileta , Church James
Published: March 2023

BACKGROUND:

Clinical experience teaches that intraperitoneal adhesions are more severe in patients with familial adenomatous polyposis than in patients without it. This impression may come from the common association of familial adenomatous polyposis with desmoid disease.

OBJECTIVES:

To determine whether patients with familial adenomatous polyposis and desmoid disease develop more severe adhesions than those without desmoid disease.

DESIGN:

Prospectively collected data study.

SETTINGS:

Hereditary colorectal cancer center in a tertiary referral hospital.

PATIENTS:

Patients undergoing first reoperative intra-abdominal surgery for familial adenomatous polyposis: controls were those having their initial abdominal surgery.

INTERVENTIONS:

Surgery and adhesiolysis.

MAIN OUTCOME MEASURES:

Presence and type of desmoid disease; presence and severity of non-desmoid intraperitoneal adhesions. Where patients had multiple operations, only the first reoperative surgery was chosen. Desmoid disease was noted as reaction (sheet) or mass. Adhesions were graded as none, mild (<10 minutes for mobilization), average (10 to 30 minutes) and severe (>30 minutes or significant bowel damage). Patients having first abdominal surgery for familial adenomatous polyposis were used as a control group.

RESULTS:

A total of 221 patients had no prior surgery: 5% had desmoids and 1% had adhesions. 137 patients underwent reoperative surgery: 39% had desmoid disease (p < 0.05 vs no prior surgery), the highest rate being in patients after ileal pouch anal anastomosis (57%), and 45% had severe adhesions (p < 0.01 vs no prior surgery), worst after Koch pouch (89%) and total proctocolectomy with ileostomy (82%). 36% of patients without desmoid disease had severe adhesions. Desmoid reaction was associated with severe adhesions in 47% of cases, and desmoid tumors were associated with severe adhesions in 66% of cases.

LIMITATIONS:

Possible limitations include the potential overlap between desmoid adhesions and non-desmoid adhesions as well as the potential for inaccuracy in defining time of adhesiolyses.

CONCLUSION:

Familial adenomatous polyposis is associated with severe postoperative adhesions after reoperative abdominal surgery, especially in patients who develop desmoid disease.
Comparative Safety of Gout Treatment Strategies on Cardiovascular Outcomes Using Observational Data: Clone-censor-weight Target Trial Emulation Approach
Authors: Yoshida Kazuki , Liu Jun , Desai Rishi J. , Glynn Robert J. , Solomon Daniel H. , Kim Seoyoung C.
Published: March 2023

Background:

We sought to examine the cardiovascular safety of intensive treat-to-target serum urate strategies for gout using Medicare claims data linked to electronic health record laboratory data.

Methods:

We selected patients with gout who initiated urate-lowering therapy. We emulated a hypothetical trial comparing the rate of major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) among seven different strategies over 24 months. Three aspects were considered in defining increasingly intensive strategies: (1) continuation of urate-lowering therapy, (2) serum urate monitoring, and (3) modification of urate-lowering therapy when serum urate >6 mg/dl. We applied the “clone-censor-weight” method to account for baseline and time-varying confounding.

Results:

We identified 4402 patients with gout who initiated urate-lowering therapy (mean age 77; male 60%). During a total of 6611 person–years (PY) of follow-up under usual care, the rate of major cardiovascular events (first and recurrent) was 4.5/100 PY (95% CI = 4.0, 5.1). The rate ratios (RRs) suggested reductions (RR point estimates 0.88–0.84) compared with usual care. All 95% CIs were imprecise, but their upper bounds excluded substantial increase in RRs. RRs were closer to 1.0 for the analysis focusing on the first major adverse cardiovascular event during follow-up and on comparison to the strategy requiring continuation of urate-lowering therapy (but not necessarily titration).

Conclusions:

Our treatment strategy trial emulation did not find increased risk of major adverse cardiovascular events with intensive urate-lowering strategies. Results may provide reassurance of the cardiovascular safety of intensive treat-to-target serum urate strategies recommended by rheumatology societies.
Corneal tissue addition keratoplasty: new intrastromal inlay procedure for keratoconus using femtosecond laser–shaped preserved corneal tissue
Authors: Greenstein Steven A. , Yu Austin S. , Gelles John D. , Eshraghi Hamoon , Hersh Peter S.
Published: March 2023

Purpose:

To report results of Corneal Tissue Addition Keratoplasty (CTAK) for keratoconus (KC) and ectasia after laser in situ keratomileusis.

Setting:

Cornea and refractive surgery practice.

Design:

Single center, prospective, open label clinical trial.

Methods:

21 eyes of 18 patients underwent CTAK. A tissue inlay of preserved corneal tissue was cut to customized specifications with a femtosecond laser and placed in a laser-created channel in the host cornea. Postoperative uncorrected and corrected distance visual acuity (UDVA, CDVA), manifest refraction spherical equivalent (MRSE), topographic mean keratometry (Kmean), maximum keratometry (Kmax), and the point of maximum flattening (Kmaxflat) were measured.

Results:

Average UDVA improved from 1.21 ± 0.35 logMAR lines (LL) (20/327) to 0.61 ± 0.25 LL (20/82) (P < .001). Average CDVA improved from 0.62 ± 0.33 LL (20/82) to 0.34 ± 0.21 LL (20/43) (P = .002), and average MRSE improved from −6.25 ± 5.45 diopters (D) to −1.61 ± 3.33 D (P = .002). Individually, 20 eyes (95.2%) gained more than 2 lines of UDVA, with 10 eyes (47.6%) gaining more than 6 lines, and no eyes worsening. 12 eyes (57.1%) gained at least 2 lines of CDVA, with 1 eye worsening by more than 2 lines. At 6 months, average Kmean flattened by −8.44 D (P = .002), Kmax flattened by −6.91 D (P = .096), and mean Kmaxflat was −16.03 D.

Conclusions:

CTAK is a promising procedure to improve visual acuity and topography in patients with KC and ectasia.
Neural processing of pain-related distress to neck-specific movements in people with chronic whiplash-associated disorders
Authors: Murillo Carlos , Coppieters Iris , Cagnie Barbara , Bernaers Lisa , Bontinck Jente , Meeus Mira , Timmers Inge
Published: March 2023

Pain-related distress contributes to long-term disability in chronic whiplash-associated disorders. Recently, neuroimaging studies have revealed altered neural responses to viewing pictures of movements associated with back pain in key regions for threat and affective processing. In this study, we examined neural correlates of imagining neck-specific movements designed to elicit pain-related distress in individuals with whiplash-associated disorders (n = 63) when compared with that in sex-matched pain-free controls (n = 32). In the scanner, participants were presented with neck-specific movement-related pictures divided into 3 categories (high fear, moderate-fear, and neutral control pictures) and asked to imagine how they would feel if they were performing the movement. Whole-brain analyses revealed greater differential activation (high-fear vs neutral) in individuals with whiplash-associated disorders when compared with that in pain-free controls in 6 clusters including right and left postcentral gyri, left parietal operculum, dorsal precuneus, left superior frontal gyrus/anterior cingulate cortex, and posterior cingulate cortex/ventral precuneus. For the contrast moderate-fear vs neutral, patients showed greater differential activation than controls in the right and left posterolateral cerebellum. Activation patterns in the precuneus and posterior cingulate cortex were negatively associated with pain-related fear, but no other correlations were observed. Together, the findings suggest that when conceptualizing neck-specific movements associated with pain, people with chronic whiplash-associated disorders may predict—and potentially amplify—their sensory and affective consequences and therewith trigger dysfunctional affective and/or behavioral responses. Herewith, we provide new insights into the neural mechanisms underlying chronic pain in people with whiplash-associated disorders, pointing towards a complex interplay between cognitive/affective and sensorimotor circuitry.
NMR foodomics in the assessment of diet and effects beyond nutrients
Authors: Bertram Hanne Christine
Published: March 2023

Purpose of review

This review provides an overview of most recent research studies employing nuclear magnetic resonance (NMR)-based metabolomics in the assessment of effects of diet and food ingestion.

Recent findings

NMR metabolomics is a useful tool in the elucidation of specific diets, for example, the Mediterranean diet, the New Nordic diet types, and also for comparing vegan, vegetarian and omnivore diets where specific diet-linked metabolite perturbations have been identified. Another core area where NMR metabolomics is employed involves research focused on examining specific food components or ingredients, including dietary fibers and other functional components. In several cases, NMR metabolomics has aided to document how specific food components exert effects on the metabolic activity of the gut microbiota. Research has also demonstrated the potential use of NMR metabolomics in assessing diet quality and interactions between specific food components such as meat and diet quality. The implications of these findings are important as they address that background diet can be decisive for if food items turn out to exert either harmful or health-promoting effects.

NMR metabolomics can provide important mechanistic insight and aid to biomarker discovery with implications for compliance and food registration purposes.
Nonceliac gluten sensitivity
Authors: Catassi Carlo , Catassi Giulia , Naspi Loris
Published: March 2023

Purpose of review

To describe recent advances on nonceliac gluten sensitivity (NCGS), a recently described disorder characterized by variable symptoms and frequent irritable bowel syndrome (IBS)-like manifestations.

Recent findings

The recent description of disease-triggering wheat components other than gluten, such as fructans and amylase-trypsin inhibitors (ATIs), definitely suggests that nonceliac wheat sensitivity (NCWS) is a better ‘umbrella‘ terminology than NCGS. Self-reported NCWS is very common worldwide, particularly in patients seen at the gastroenterology clinic, but many of these diagnoses are not confirmed by standard clinical criteria. A biomarker of NCWS is still lacking, however, subtle histological features at the small intestinal biopsy may facilitate diagnosis. Treatment of NCWS is based on the gluten-free diet (GFD). The GFD has proven to be an effective treatment of a significant proportion of NCWS-related IBS patients. Dietary therapies for IBS, including the GFD, should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Pioneer studies are under way to test the therapeutic efficacy of supplemental gluten-digesting enzyme preparations in patients with NCWS.

Recent studies highlight interesting pathophysiological and clinical features of NCWS. Many questions remain, however, unanswered, such as the epidemiology, a biomarker(s), and the natural history of this clinical entity.
Bempedoic acid for nonalcoholic fatty liver disease: evidence and mechanisms of action
Authors: Roglans Núria , Laguna Juan Carlos , Alegret Marta
Published: March 2023

Purpose of review

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent progressive condition that lacks a specific pharmacological treatment. ATP-citrate lyase (ACLY) is one of the emergent targets for the treatment of NAFLD. This review aims to summarize the role of ACLY in NAFLD, provide evidence of the beneficial effects of the ACLY inhibitor bempedoic acid (BemA) in NAFLD and discuss the mechanisms involved.

Recent findings

BemA is effective in reducing hepatic steatosis in several animal models that recapitulate different stages of the disease. Thus, in a dietary model of simple hepatic steatosis in female rats, BemA abrogates the accumulation of liver fat. Apart from ACLY inhibition, BemA has several functions in the liver that contribute to the antisteatotic effect: inhibition of ketohexokinase, induction of patatin-like phospholipase domain-containing protein 3 and increases in both fatty acid β-oxidation activity and hepatic H2S production. In models of the advanced phases of NAFLD, BemA reduces not only steatosis, but also ballooning, lobular inflammation and hepatic fibrosis, by mechanisms involving both hepatocytes and hepatic stellate cells.

BemA, an ACLY inhibitor currently approved for the treatment of hypercholesterolemia, may be a useful drug to treat NAFLD through its antisteatotic, anti-inflammatory and antifibrotic effects.
A Scoping Review of Compassion Fatigue Among Oncology Nurses Caring for Adult Patients
Authors: Banks Janneka , Lopez Violeta , Sahay Ashlyn , Cleary Michelle
Published: March 2023

Background

Oncology nurses have frequent contact with oncology patients during their cancer journey. This long-term, recurrent contact can impact the health and well-being of the nurse through the development of compassion fatigue (CF).

Objectives

To identify what contributes to CF and what individual, interpersonal, and organizational factors mitigate CF among oncology nurses caring for adult patients.

Methods

A scoping review framework by Arksey and O’Malley guided this review. Electronic databases were searched for relevant studies. A blinded screening process was undertaken by the authors using the following inclusion criteria: English language published from January 2011 to December 2021, primary research peer-reviewed studies, and focusing on CF within oncology nurses caring for adult patients in any practice setting.

Results

Nineteen studies (21 articles) were identified. The review found nurses’ personal beliefs around nursing care being provided, and personality traits of psychological inflexibility, neuroticism, passive coping, and avoidance contributed to CF. Workplace conflict and lack of a healthy work-life balance also contributed to CF. However, nurses’ personal resilience, ability to positively reflect upon their work, a supportive team environment, and continuing education were found to mitigate CF.

Conclusions

Levels of CF vary among oncology nurses caring for adult patients. Oncology nurses may benefit from personal and organizational resources aimed at improving oncology nurses’ professional quality of life while decreasing CF.

Implications for Practice

Consideration and future research of effective interventions are needed to sustain a future health workforce and mitigate CF among oncology nurses.
High Prevalence of Rectal Chlamydia and Gonorrhea Among Men Who Have Sex With Men Who Do Not Engage in Receptive Anal Sex
Authors: Khosropour Christine M. , Coomes David M. , LeClair Angela , Saechao Farchung , Vorn Seila , Soge Olusegun O. , Barbee Lindley A.
Published: March 2023

Background

In the United States, annual screening for rectal gonorrhea and chlamydia is only recommended for men who report receptive anal sex (RAS), but other behaviors (e.g., rimming) may lead to rectal Chlamydia trachomatis and Neisseria gonorrhoeae acquisition.

Methods

We enrolled individuals assigned male sex at birth who reported sex with men and denied RAS in the past 2 years or reported RAS 1 to 2 years ago but were tested and treated since last RAS. Participants enrolled in-person at the Sexual Health Clinic in Seattle, Washington (December 2019–July 2022), or online (July 2021–March 2022). Participants completed a survey that asked about 13 non-RAS behaviors and self-collected a rectal swab for gonorrhea/chlamydia nucleic acid amplification testing. We used log binomial regression to estimate the prevalence of rectal gonorrhea/chlamydia (adjusted prevalence ratio [aPR]) by behavior, adjusting for all other behaviors.

Results

We enrolled 292 participants (247 in-person and 45 online); 277 (95%) had nucleic acid amplification testing results. Rectal gonorrhea/chlamydia test positivity was 14.1% overall: 10.5% for rectal chlamydia and 4.3% for rectal gonorrhea. Most participants (70%) reported ≥1 behavior that involved direct contact with their anus. We observed a higher risk of rectal chlamydia for those who did versus did not report perianal play at 12 months (aPR, 2.39; 95% confidence interval, 1.10–5.22) and 2 months (aPR, 2.21; 95% confidence interval, 1.02–4.79). This was the only behavior significantly associated with testing positive.

Conclusions

Rectal C. trachomatis and N. gonorrhoeae prevalence was high among men who deny RAS, suggesting other possible routes of acquisition. Rectal screening for those who deny RAS should be made with careful consideration of individual- and population-level effects.
Embedding a Dedicated Sexual Health Clinic in a University's Health Services Expands Sexually Transmitted Infection Screening Options
Authors: Camino Andres F. , Whitfield Meghan , Pridgen Kathleen , Van Der Pol Barbara , Van Wagoner Nicholas
Published: March 2023

Background

The primary objectives of this study were to assess utilization of sexual health services at a university's student health and wellness center and to determine whether the presence of a dedicated sexual health clinic (SHC) was associated with different utilization patterns for sexual health services when compared with primary care clinics.

Methods

This was a retrospective chart review of patients presenting to the University of Alabama at Birmingham's Student Health and Wellness Center for sexual health services between January 2015 and June 2019. Utilization of sexual health services, specifically sexually transmitted infection (STI) testing, was compared between the dedicated SHC and primary care clinics.

Results

A total of 3081 cases were included. There were statistically significant differences in the proportion of male individuals and populations more burdened by STI tested for STI in the SHC (i.e., persons who identify as Black and younger female individual). We also observed a higher percentage of positive gonorrhea and chlamydia test results and a greater likelihood of extragenital screening in men who have sex with men in the SHC.

Conclusions

The dedicated SHC within the University of Alabama at Birmingham's Student Health and Wellness Center was associated with an increase in STI screenings. There was a significant difference between the demographics of those presenting to the SHC versus primary care clinics, proportionally more diagnoses of gonorrhea and chlamydia, and, for men who have sex with men, more extragenital screenings performed in the SHC. These findings suggest that there may be a benefit of an embedded SHC in college and university health and wellness centers.
Bibliometric Analysis of Authorship of Publications about Sub-Saharan Africa Published in the Journal Sexually Transmitted Diseases, 2011-2020
Authors: Akudinobi Ezinne A. , Rietmeijer Cornelis A. , Ndowa Francis J. , Kilmarx Peter H.
Published: March 2023

Background

As a potential indicator of equity in research partnerships, we conducted a bibliometric analysis of author affiliations and author order in publications about sub-Saharan Africa published in the journal Sexually Transmitted Diseases.

Methods

We identified articles in the journal Sexually Transmitted Diseases that were about sub-Saharan Africa and published from 2011 to 2020. Medical Subject Heading (MeSH) terms in PubMed were used to identity articles about sub-Saharan Africa. Authors with at least one affiliation in sub-Saharan Africa were characterized as sub-Saharan Africa-affiliated authors.

Results

Of the 1,439 articles that were published in Sexually Transmitted Diseases from 2011 to 2020, 148 (10%) had a MeSH term for a sub-Saharan African country. Of the 604 authors of these 148 articles, 53 (36%) of the first authors, 493 (53%) of the middle authors, and 58 (40%) of the last authors had a sub-Saharan African affiliation; 13 (8.8%) of the articles had no authors with a sub-Saharan African affiliation. The proportions of sub-Saharan African-affiliated authors in first and last authorship positions did not change significantly from 2011-15 (77 articles) to 2016-20 (71 articles).

Conclusions

The underrepresentation of Africans in first and last authorship positions suggests power imbalances in global scientific partnerships. Funders, researchers, editors, publishers, and grant and manuscript reviewers each have roles in promoting equity in global health research. This study may serve as an example for journals to establish benchmarks and monitor progress toward a more equitable research environment.
Collateral Impacts of the COVID-19 Pandemic: The New York City Experience
Authors: Davies Emily G. , Gould L. Hannah , Le Karolyn , Helmy Hannah , Lall Ramona , Li Wenhui , Mathes Robert , Levanon Seligson Amber , Van Wye Gretchen , Chokshi Dave A.
Published: March 2023

Objective:

To adapt an existing surveillance system to monitor the collateral impacts of the COVID-19 pandemic on health outcomes in New York City across 6 domains: access to care, chronic disease, sexual/reproductive health, food/economic insecurity, mental/behavioral health, and environmental health.

Design:

Epidemiologic assessment. Public health surveillance system.

Setting:

New York City.

Participants:

New York City residents.

Main Outcome Measures:

We monitored approximately 30 indicators, compiling data from 2006 to 2022. Sources of data include clinic visits, surveillance surveys, vital statistics, emergency department visits, lead and diabetes registries, Medicaid claims, and public benefit enrollment.

Results:

We observed disruptions across most indicators including more than 50% decrease in emergency department usage early in the pandemic, which rebounded to prepandemic levels by late 2021, changes in reporting levels of probable anxiety and depression, and worsening birth outcomes for mothers who identified as Asian/Pacific Islander or Black. Data are processed in SAS and analyzed using the R Surveillance package to detect possible inflections. Data are updated monthly to an internal Tableau Dashboard and shared with agency leadership.

Conclusions:

As the COVID-19 pandemic continues into its third year, public health priorities are returning to addressing non–COVID-19-related diseases and conditions, their collateral impacts, and postpandemic recovery needs. Substantial work is needed to return even to a suboptimal baseline across multiple health topic areas. Our surveillance framework offers a valuable starting place to effectively allocate resources, develop interventions, and issue public communications.
Policy Opportunities and Legal Considerations to Reform SNAP-Authorized Food Retail Environments
Authors: Pomeranz Jennifer L.
Published: March 2023

Context:

There is an invigorated national interest in nutrition security, with emphasis on the Supplemental Nutrition Assistance Program (SNAP) playing a key role.

Objective:

To support healthy food purchasing, several strategies have emerged to modify the food retail environment. However, the legal feasibility of several such policy options has not been established.

Design:

Research was conducted using Lexis+ to evaluate statutes, regulations, and case law to determine the legal feasibility of requiring retail-based SNAP signage and nutrition disclosures, healthy endcaps and checkout aisles, and tying advertising restrictions to the licensing of SNAP retailers.

Setting:

US in-store and online food retail retailers.

Main Outcome Measure:

Legal feasibility.

Results:

Requiring retailers that designate certain foods or locations as SNAP-eligible to consistently do so in all SNAP-eligible pages/locations is likely feasible. If properly drafted to focus on the nutritional quality of food, healthy checkout and endcap restrictions are legally feasible. It is of unclear legal feasibility to require retailers (especially in-store) to disclose nutrition-related labeling, shelf tags, or nonfactual symbols indicating the relative healthfulness of products. Restricting or banning advertising is not legally feasible even if the government ties the restrictions to retail licensing requirements.

Conclusions:

Entities seeking to support healthy food retail should not seek to restrict advertising or compel retailers to convey messages against their interests. The government can license retailers and require them to abide by laws and other requirements that do not violate their constitutional rights. The government can also use its own speech through public service announcements, billboards, and transit advertising to encourage healthy food consumption for all shoppers including those who use SNAP. Additional research is warranted into online retail practices to evaluate variations in online checkout pages and to determine whether online retailers treat SNAP participants differently from non-SNAP participants.
Discrimination of Liver Metastases of Digestive System Neuroendocrine Tumors From Neuroendocrine Carcinoma by Computed Tomography–Based Radiomics Analysis
Authors: Gu Xiao-Lei , Cui Yong , Zhu Hai-Tao , Li Xiao-Ting , Pei Xiang , He Xiao-Xiao , Yang Li , Lu Ming , Li Zhong-Wu , Sun Ying-Shi
Published: March 2023

Objective

The aim of the study is to investigate the value of computed tomography (CT) radiomics features to discriminate the liver metastases (LMs) of digestive system neuroendocrine tumors (NETs) from neuroendocrine carcinoma (NECs).

Methods

Ninety-nine patients with LMs of digestive system neuroendocrine neoplasms from 2 institutions were included. Radiomics features were extracted from the portal venous phase CT images by the Pyradiomics and then selected by using the t test, Pearson correlation analysis, and least absolute shrinkage and selection operator method. The radiomics score (Rad score) for each patient was constructed by linear combination of the selected radiomics features. The radiological model was constructed by radiological features using the multivariable logistic regression. Then, the combined model was constructed by combining Rad score and the radiological model into logistic regression. The performance of all models was evaluated by the receiver operating characteristic curves with the area under curve (AUC).

Results

In the radiological model, only the enhancement degree (odds ratio, 8.299; 95% confidence interval, 2.070–32.703; P = 0.003) was an independent predictor for discriminating the LMs of digestive system NETs from those of NECs. The combined model constructed by the Rad score in combination with the enhancement degree showed good discrimination performance, with AUCs of 0.893, 0.841, and 0.740 in the training, testing, and external validation groups, respectively. In addition, it performed better than radiological model in the training and testing groups (AUC, 0.893 vs 0.726; AUC, 0.841 vs 0.621).

Conclusions

The CT radiomics might be useful for discrimination LMs of digestive system NECs from NETs.
RIGHT VENTRICULAR DYSFUNCTION IN SEPSIS: AN UPDATED NARRATIVE REVIEW
Authors: Bansal Mridul , Mehta Aryan , Machanahalli Balakrishna Akshay , Kalyan Sundaram Arvind , Kanwar Ardaas , Singh Mandeep , Vallabhajosyula Saraschandra
Published: March 2023

Sepsis is a multisystem disease process, which constitutes a significant public health challenge and is associated with high morbidity and mortality. Among other systems, sepsis is known to affect the cardiovascular system, which may manifest as myocardial injury, arrhythmias, refractory shock, and/or septic cardiomyopathy. Septic cardiomyopathy is defined as the reversible systolic and/or diastolic dysfunction of one or both ventricles. Left ventricle dysfunction has been extensively studied in the past, and its prognostic role in patients with sepsis is well documented. However, there is relatively scarce literature on right ventricle (RV) dysfunction and its role. Given the importance of timely detection of septic cardiomyopathy and its bearing on prognosis of patients, the role of RV dysfunction has come into renewed focus. Hence, through this review, we sought to describe the pathophysiology of RV dysfunction in sepsis and what have we learnt so far about its multifactorial nature. We also elucidate the roles of different biomarkers for its detection and prognosis, along with appropriate management of such patient population.
Perioperative Safety of Bladder Hydrodistention in Patients on Antithrombotic Therapy
Authors: Peng Liao , Wang Wei , Gao Xiao-shuai , Luo De-yi
Published: March 2023

Importance

Bladder hydrodistention (BH) is commonly used to diagnose and treat patients with interstitial cystitis/bladder pain syndrome (IC/BPS), but the overall assessment of bleeding complications for patients taking antithrombotics is lacking.

Objectives

The study aimed to investigate if perioperative complications were more common in patients with IC/BPS receiving antithrombotic therapy after BH.

Study design

We retrospectively reviewed patients with IC/BPS who underwent hydrodistention during January 2010 and May 2021. Patients with and without antithrombotic drugs were identified and grouped, and their medical records were reviewed. Perioperative data and symptom scores were assessed. The rates of complications in the 2 groups were recorded at 3 months and at the last visit postoperatively.

Results

A total of 387 patients were eventually included. Among them, 29 (7.5%) patients were receiving systemic antithrombotic therapy and 358 (92.5%) were not. Compared with the non-antithrombotic group, patients receiving antithrombotic therapy demonstrated a longer hospital stay (P = 0.033) and a longer catheterization time (P = 0.034). Moreover, the patients with antithrombotic drugs had increased odds of bladder tamponade (odds ratio, 6.76; P = 0.019) and urinary retention (odds ratio, 5.79; P = 0.033) both 3 months postoperatively and last follow-up, but this is not statistically different between patients with and without Hunner lesions. No thromboembolic events were identified during the study period.

Conclusions

Although a small number of patients with IC/BPS needed anticoagulants, longer hospital stays, longer catheterization time, and increased odds of bladder tamponade and urinary retention were observed in patients receiving antithrombotic therapy. Still, a comprehensive management scheme to balance bleeding complications and antithrombotic agents is needed for individuals.
Ensemble and Iterative Engineering for Maximized Bioconversion to the Blue Pigment, Indigoidine from Non-Canonical Sustainable Carbon Sources
Authors: Eng Thomas T , Banerjee Deepanwita , Menasalvas Javier , Chen Yan , Gin Jennifer , Choudhary Hemant , Baidoo Edward , Chen Jian Hua , Ekman Axel , Kakumanu Ramu , Diercks Yuzhong Liu , Codik Alex , Larabell Carolyn , Gladden John , Simmons Blake A , Keasling Jay D , Petzold Christopher J , Mukhopadhyay Aindrila
Published: March 2023

While many heterologous molecules can be produced at trace concentrations via microbial bioconversion processes, maximizing their titers, rates, and yields from lignin-derived carbon streams remains challenging. Growth coupling can not only increase titers and yields but also shift the production period from stationary phase to growth phase. These methods for designing growth-coupling strains however require multi-gene edits for implementation which may be perceived as impractical. Here, we computationally evaluated 4,114 potential solutions for growth couplingpara-coumarate to indigoidine production and prototype two cut sets inPseudomonas putidaKT2440. We used adaptive laboratory evolution (ALE) on the initial triple deletion strain to restore growth onp-CA. Using X-ray tomography on this post-ALE strain we revealed increased cell density and decreased cell volume. Proteomics identified upregulated peroxidases that mitigate reactive oxygen species formation. Nine iterative stepwise modifications further informed by model-guided and rational approaches realized a growth coupled strain that produced 7.3 g/L indigoidine at 77% MTY inpara-coumarate minimal media. These ensemble strategies provide a blueprint for producing target molecules at high product titers, rates, and yields.
On quantum computing and geometry optimization
Authors: Malik Ashar J. , Verma Chandra S.
Published: March 2023

Quantum computers have demonstrated advantage in tackling problems considered hard for classical computers and hold promise for tackling complex problems in molecular mechanics such as mapping the conformational landscapes of biomolecules. This work attempts to explore a few ways in which classical data, relating to the Cartesian space representation of biomolecules, can be encoded for interaction with empirical quantum circuits not demonstrating quantum advantage. Using the quantum circuit in a variational arrangement together with a classical optimizer, this work deals with the optimization of spatial geometries with potential application to molecular assemblies. Additionally this work uses quantum machine learning for protein side-chain rotamer classification and uses an empirical quantum circuit for random state generation for Monte Carlo simulation for side-chain conformation sampling. Altogether, this novel work suggests ways of bridging the gap between conventional problems in life sciences and how potential solutions can be obtained using quantum computers. It is hoped that this work will provide the necessary impetus for wide-scale adoption of quantum computing in life sciences.
Highly Parallel Tissue Grafting for Combinatorial In Vivo Screening
Authors: O’Connor Colleen E. , Neufeld Anna , Fortin Chelsea L. , Johansson Fredrik , Mene Jonathan , Saxton Sarah H. , Simmonds Susana P. , Kopyeva Irina , Gregorio Nicole E. , DeForest Cole A. , Witten Daniela M. , Stevens Kelly R.
Published: March 2023

Material- and cell-based technologies such as engineered tissues hold great promise as human therapies. Yet, the development of many of these technologies becomes stalled at the stage of pre-clinical animal studies due to the tedious and low-throughput nature ofin vivoimplantation experiments. We introduce a ‘plug and play’in vivoscreening array platform called Highly Parallel Tissue Grafting (HPTG). HPTG enables parallelizedin vivoscreening of 43 three-dimensional microtissues within a single 3D printed device. Using HPTG, we screen microtissue formations with varying cellular and material components and identify formulations that support vascular self-assembly, integration and tissue function. Our studies highlight the importance of combinatorial studies that vary cellular and material formulation variables concomitantly, by revealing that inclusion of stromal cells can “rescue” vascular self-assembly in manner that is material-dependent. HPTG provides a route for accelerating pre-clinical progress for diverse medical applications including tissue therapy, cancer biomedicine, and regenerative medicine.
COMT inhibitor tolcapone represses the migration and invasion of trophoblast and results in preeclampsia-like phenotypes in mice with the modulation of EMT signaling
Authors: Chen Lu , Li Yuexia , Pang Menglan , Jie Qiuling , Sun Fei , Huang Liping , Ma Yanlin , Wu Fei , Yue Xiaojing
Published: March 2023

Pregnancy in young-onset Parkinson’s disease (YOPD) is rare; however, medication for this condition is critical for maternal and fetal health. Tolcapone is an effective antiparkinsonian drug. However, its safety studies on mothers and fetuses are limited. In this study, we aimed to investigate the effects of tolcapone on the mother and the developing fetus during different stages of gestation. Tolcapone was administered to pregnant mice at a dose of 60 (H-Tol) or 30 mg/kg/day (L-Tol) during early or mid-gestation. We observed that tolcapone administration during early gestation causes abortion and delays fetal development in a dose-dependent manner. During mid-gestation tolcapone barely caused embryo lethality; however, the mice developed preeclampsia-like phenotypes, including maternal hypertension, proteinuria, and fetal growth restriction. Histomorphological analysis of placentas from tolcapone treated mice revealed abnormalities in the trophoblast layer and the impaired trophoblast invasion in the decidua. Mechanistically, we revealed that tolcapone inhibits the invasion and migration of trophoblastsin vitro, with changes in the protein expression of Snail, Twist, and E-cadherin. In conclusion, tolcapone caused embryo lethality and growth restriction during early gestation, whereas it caused preeclampsia-like phenotypes in mice with defective trophoblast invasion in mid-gestation. Collectively, our study provides novel insights into the effects of tolcapone on pregnancy.
Integrative proteomics and transcriptomics of human T-cells reveals temporal metabolic reprogramming following TCR-induced activation
Authors: Weerakoon Harshi , Mohamed Ahmed , Wong Yide , Senadheera Bhagya , Haigh Oscar , Watkins Thomas S. , Kazakoff Stephen , Mukhopadhyay Pamela , Mulvenna Jason , Miles John J. , Hill Michelle M. , Lepletier Ailin
Published: March 2023

T-cells are critical components of the adaptive immune system. Upon activation, they acquire effector functions through a complex interplay between mRNA transcripts and proteins, the landscape of which remains to be fully elucidated. In this resource article, we present an integrative temporal proteomic and transcriptomic analysis of primary human CD4+and CD8+T-cells followingex vivoactivation with anti-CD3/CD28 Dynabeads. Our data reveal a time-dependent dissociation between the T-cell transcriptome and proteome during activation. A transient downregulation of GLUT1, the central glucose transporter in T-cells, marked the onset of reprogramming in both CD4+and CD8+T-cells. At late activation, CD4+T-cells upregulated enzymes associated with degradation of fatty acids while CD8+T-cells preferentially upregulated enzymes in the metabolism of cofactors and vitamins. Surprisingly, we found that activated CD4+and CD8+T-cells became transcriptionally more divergent at the same time their proteome became more similar. In addition to the metabolic reprogramming highlighted in our analysis, this dataset provides a public resource for understanding temporal molecular changes governing the acquisition of effector functions by T-cells.
ENLIGHT Consensus Checklist and Guidelines for reporting laboratory studies on the non-visual effects of light in humans
Authors: Spitschan Manuel , Kervezee Laura , Lok Renske , McGlashan Elise , Najjar Raymond P. ,   the ENLIGHT Consortium
Published: March 2023

Beyond vision, light has wide-reaching effects on human health and well-being. However, there is no consensus on reporting light characteristics in studies investigating non-visual responses to light. This project aimed at developing a reporting checklist for laboratory-based investigations on the impact of light on non-visual physiology. To this end, a four-step modified Delphi process (three questionnaire-based feedback rounds and one face-to-face group discussion) involving international experts was conducted. Across these four rounds, an initial list of 61 items related to reporting light-based interventions was condensed to a final checklist containing 25 items, based upon consensus among experts (final n=60). Nine of these items were determined to be necessary to report regardless of the specific research question or context. A description of each item was provided in the accompanying guidelines. Most participants (92%) reported being satisfied or very satisfied with the consensus process, checklist, and guidelines. The ENLIGHT Checklist and Guidelines are the first consensus-based guidelines for documenting and reporting ocular light-based interventions for human studies. The implementation of the checklist and guidelines will enhance the impact of light-based research by ensuring comprehensive documentation and reproducibility and enabling data aggregation across studies.
Relating Polar Bears Killed, Human Presence, and Ice Conditions in Svalbard 1987 – 2019
Authors: Vongraven D. , Amstrup S.C. , McDonald T.L. , Mitchell J. , Yoccoz N.G.
Published: March 2023

Conflicts between humans and polar bears have been predicted to increase as polar bear prime habitat, sea ice, is decreasing. In Svalbard, a strong protection and strict control schemes have secured near complete records of bears killed and found dead since 1987. We analyzed the trend in the number of kills and related this to human visitation to the island. We found a slight decrease in the number of kills in the period 1987-2019, and a decrease in per capita number of kills when monthly kills were compared to the monthly number of visitors disembarking in the main settlement. We then used a discrete choice resource selection model to assess whether polar bear kill events are related to attributes of the kill sites and environmental conditions at the time. We divided Svalbard in four sectors, North, East, South, and West, and monthly average ice cover was calculated in 25-km rings around Svalbard, rings that were further delineated by the four sectors. We found that the odds of a kill was greater along the shoreline, and that the odds would be reduced by 50% when moving only 900 m from the shoreline when all sectors were included. Distance from other covariates like settlements, trapper’s cabins, and landing sites for tourists did for the most part not have a significant impact on the odds of a kill. Sectorwise, ice cover had no significant impact on the odds for a kill. The decreasing trend in kills of polar bears might partly be explained by the success of strict protection and management regimes of Svalbard wilderness.
A 3D-printed flow-cell for on-grid purification of electron microscopy samples directly from lysate
Authors: Ramlaul Kailash , Feng Ziyi , Canavan Caoimhe , Natàlia de Garrido Martín , Carreño David , Crone Michael , Jensen Kirsten E. , Li Bing , Barnet Harry , Riglar David T. , Freemont Paul S. , Miller David , Aylett Christopher H. S.
Published: March 2023

While recent advances in cryo-EM, coupled with single particle analysis, have the potential to allow structure determination in a near-native state from vanishingly few individual particles, this vision has yet to be realised in practise. Requirements for particle numbers that currently far exceed the theoretical lower limits, challenges with the practicalities of achieving high concentrations for difficult-to-produce samples, and inadequate sample-dependent imaging conditions, all result in significant bottlenecks preventing routine structure determination using cryo-EM. Therefore, considerable efforts are being made to circumvent these bottlenecks by developing affinity purification of samples on-grid; at once obviating the need to produce large amounts of protein, as well as more directly controlling the variable, and sample-dependent, process of grid preparation.

In this proof-of-concept study, we demonstrate a further practical step towards this paradigm, developing a 3D-printable flow-cell device to allow on-grid affinity purification from raw inputs such as whole cell lysates, using graphene oxide-based affinity grids. Our flow-cell device can be interfaced directly with routinely-used laboratory equipment such as liquid chromatographs, or peristaltic pumps, fitted with standard chromatographic (1/16”) connectors, and can be used to allow binding of samples to affinity grids in a controlled environment prior to the extensive washing required to remove impurities. Furthermore, by designing a device which can be 3D printed and coupled to routinely used laboratory equipment, we hope to increase the accessibility of the techniques presented herein to researchers working towards single-particle macromolecular structures.
SPLASH2 provides ultra-efficient, scalable, and unsupervised discovery on raw sequencing reads
Authors: Kokot Marek , Dehghannasiri Roozbeh , Baharav Tavor , Salzman Julia , Deorowicz Sebastian
Published: March 2023

SPLASH is an unsupervised, reference-free, and unifying algorithm that discovers regulated sequence variation through statistical analysis ofk-mer composition, subsuming many application-specific methods. Here, we introduce SPLASH2, a fast, scalable implementation of SPLASH based on an efficientk-mer counting approach. SPLASH2 enables rapid analysis of massive datasets from a wide range of sequencing technologies and biological contexts, delivering unparalleled scale and speed. The SPLASH2 algorithm unveils new biology (without tuning) in single-cell RNA-sequencing data from human muscle cells, as well as bulk RNA-seq from the entire Cancer Cell Line Encyclopedia (CCLE), including substantial unannotated alternative splicing in cancer transcriptome. The same untuned SPLASH2 algorithm recovers the BCR-ABL gene fusion, and detects circRNA sensitively and specifically, underscoring SPLASH2’s unmatched precision and scalability across diverse RNA-seq detection tasks.
Multiple cancer types rapidly escape from multiple MAPK inhibitors to generate mutagenesis-prone subpopulations
Authors: Hoffman Timothy E. , Yang Chen , Nangia Varuna , Ill C. Ryland , Spencer Sabrina L.
Published: March 2023

Many cancers harbor pro-proliferative mutations of the mitogen-activated protein kinase (MAPK) pathway and many targeted inhibitors now exist for clinical use, but drug resistance remains a major issue. We recently showed that BRAF-driven melanoma cells treated with BRAF inhibitors can non-genetically adapt to drug within 3-4 days to escape quiescence and resume slow proliferation. Here we show that this phenomenon is not unique to melanomas treated with BRAF inhibitors but rather is widespread across many clinical MAPK inhibitors and cancer types driven by EGFR, KRAS, and BRAF mutations. In all treatment contexts examined, a subset of cells can escape drug-induced quiescence within four days to resume proliferation. These escapee cells broadly experience aberrant DNA replication, accumulate DNA lesions, spend longer in G2-M cell cycle phases, and mount an ATR-dependent stress response. We further identify the Fanconi anemia (FA) DNA repair pathway as critical for successful mitotic completion in escapees. Long-term cultures, patient samples, and clinical data demonstrate a broad dependency on ATR- and FA-mediated stress tolerance. Together, these results highlight the pervasiveness with which MAPK-mutant cancers are able to rapidly escape drug and the importance of suppressing early stress tolerance pathways to potentially achieve more durable clinical responses to targeted MAPK pathway inhibitors.
Mechanisms of transcription control by distal enhancers from high-resolution single-gene imaging
Authors: Cheng Lingling , De Chayan , Li Jieru , Pertsinidis Alexandros
Published: March 2023

How distal enhancers physically control promoters over large genomic distances, to enable cell-type specific gene expression, remains obscure. Using single-gene super-resolution imaging and acute targeted perturbations, we define physical parameters of enhancer-promoter communication and elucidate processes that underlie target gene activation. Productive enhancer-promoter encounters happen at 3D distances δ200 nm - a spatial scale corresponding to unexpected enhancer-associated clusters of general transcription factor (GTF) components of the Pol II machinery. Distal activation is achieved by increasing transcriptional bursting frequency, a process facilitated by embedding a promoter into such GTF clusters and by accelerating an underlying multi-step cascade comprising early phases in the Pol II transcription cycle. These findings help clarify molecular/biochemical signals involved in long-range activation and their means of transmission from enhancer to promoter.