bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting cosmological filaments at high redshifts: emergence of spaghetti-type flow inside DM haloes
Authors: Bi Da , Shlosman Isaac , Romano-Díaz Emilio
Published: December 2023

We use high-resolution zoom-in simulations to study the fueling of central galaxies by filamentary and diffuse accretion at redshifts, z ≳ 2. The parent haloes were chosen with similar total masses, log (Mvir/M⊙) ∼ 11.75 ± 0.05, at z = 6, 4, and 2, in high/low overdensity environments. We analyse the kinematic and thermodynamic properties of circumgalactic medium (CGM) within few virial radii, Rvir, and down to the central galaxy. Using a hybrid d-web/entropy method we mapped the gaseous filaments, and separated inflows from outflows. We find that (1) The CGM is multiphase and not in thermodynamic or dynamic equilibrium; (2) filamentary and diffuse accretion rates and densities decrease with lower redshifts, and inflow velocities decrease from $200-300\, {\rm {km\, s}^{-1}}$ by a factor of 2; (3) temperature within the filaments increases inside Rvir, faster at lower redshifts; (4) filaments show a complex structure along their spines: a core radial flow surrounded by a lower density envelope. The cores exhibit elevated densities and lower temperature, with no obvious metallicity gradient in the cross sections. Filaments also tend to separate into different infall velocity regions and split density cores, thus producing a spaghetti-type flow; (6) inside the inner $\sim 30\, h^{-1}$ kpc, filaments develop the Kelvin–Helmholtz instability which ablates and dissolves them, and triggers turbulence along the filaments, clearly delineating their spines; (7) finally, the galactic outflows affect mostly the inner ∼0.5Rvir ∼ 100 h−1 kpc of the CGM.
The frequency and sizes of inner bars and nuclear rings in barred galaxies and their dependence on galaxy properties
Authors: Erwin Peter
Published: December 2023

Using a volume- and mass-limited (D < 30 Mpc, $\log \, (M_{\star }/M_{\odot })\ge 9.75$) sample of 155 barred S0–Sd galaxies, I determine the fraction with secondary structures within their bars. Some 20 ± 3 per cent have a separate inner bar, making them double-barred; an identical fraction have nuclear rings, with $11^{+3}_{-2}$ per cent hosting both. The inner-bar frequency is a strong, monotonic function of stellar mass: only $4^{+3}_{-2}$ per cent of barred galaxies with $\log \, (M_{\star }/M_{\odot })= 9.75$–10.25 are double-barred, while 47 ± 8 per cent of those with $\log \, (M_{\star }/M_{\odot })\gt 10.5$ are. The nuclear-ring frequency is a strong function of absolute bar size: only $1^{+2}_{-1}$ per cent of bars with semimajor axes <2 kpc have nuclear rings, while $39^{+6}_{-5}$ per cent of larger bars do. Both inner bars and nuclear rings are absent in very late-type (Scd–Sd) galaxies. Inner bar size correlates with galaxy stellar mass, but is clearly offset to smaller sizes from the main population of bars. This makes it possible to define ‘nuclear bars’ in a consistent fashion, based on stellar mass. There are eight single-barred galaxies where the bars are nuclear-bar-sized; some of these may be systems where an outer bar failed to form, or previously double-barred galaxies where the outer bar has dissolved. Inner bar size is even more tightly correlated with host bar size, which is likely the primary driver. In contrast, nuclear ring size is only weakly correlated with galaxy mass or bar size, with more scatter in size than is true of inner bars.
Fracture and relaxation in dense cornstarch suspensions
Authors: Lilin Paul , Elkhoury Jean E , Peters Ivo R , Bischofberger Irmgard
Published: December 2023

Dense suspensions exhibit the remarkable ability to switch dynamically and reversibly from a fluid-like to a solid-like, shear-jammed (SJ) state. Here, we show how this transition has important implications for the propensity for forming fractures. We inject air into bulk dense cornstarch suspensions and visualize the air invasion into the opaque material using time-resolved X-ray radiography. For suspensions with cornstarch mass fractions high enough to exhibit discontinuous shear thickening and shear jamming, we show that air injection leads to fractures in the material. For high mass fractions, these fractures grow quasistatically as rough cavities with fractured interfaces. For lower mass fractions, remarkably, the fractures can relax to smooth bubbles that then rise under buoyancy. We show that the onset of the relaxation occurs as the shear rate induced by the air cavity growth decreases below the critical shear rate denoting the onset of discontinuous shear thickening, which reveals a structural signature of the SJ state.
Mechanisms for cardiac calcium pump activation by its substrate and a synthetic allosteric modulator using fluorescence lifetime imaging
Authors: Šeflová Jaroslava , Cruz-Cortés Carlos , Guerrero-Serna Guadalupe , Robia Seth L , Espinoza-Fonseca L Michel
Published: December 2023

The discovery of allosteric modulators is an emerging paradigm in drug discovery, and signal transduction is a subtle and dynamic process that is challenging to characterize. We developed a time-correlated single photon-counting imaging approach to investigate the structural mechanisms for small-molecule activation of the cardiac sarcoplasmic reticulum Ca2+-ATPase, a pharmacologically important pump that transports Ca2+ at the expense of adenosine triphosphate (ATP) hydrolysis. We first tested whether the dissociation of sarcoplasmic reticulum Ca2+-ATPase from its regulatory protein phospholamban is required for small-molecule activation. We found that CDN1163, a validated sarcoplasmic reticulum Ca2+-ATPase activator, does not have significant effects on the stability of the sarcoplasmic reticulum Ca2+-ATPase–phospholamban complex. Time-correlated single photon-counting imaging experiments using the nonhydrolyzable ATP analog β,γ-Methyleneadenosine 5′-triphosphate (AMP-PCP) showed ATP is an allosteric modulator of sarcoplasmic reticulum Ca2+-ATPase, increasing the fraction of catalytically competent structures at physiologically relevant Ca2+ concentrations. Unlike ATP, CDN1163 alone has no significant effects on the Ca2+-dependent shifts in the structural populations of sarcoplasmic reticulum Ca2+-ATPase, and it does not increase the pump's affinity for Ca2+ ions. However, we found that CDN1163 enhances the ATP-mediated modulatory effects to increase the population of catalytically competent sarcoplasmic reticulum Ca2+-ATPase structures. Importantly, this structural shift occurs within the physiological window of Ca2+ concentrations at which sarcoplasmic reticulum Ca2+-ATPase operates. We demonstrated that ATP is both a substrate and modulator of sarcoplasmic reticulum Ca2+-ATPase and showed that CDN1163 and ATP act synergistically to populate sarcoplasmic reticulum Ca2+-ATPase structures that are primed for phosphorylation. This study provides novel insights into the structural mechanisms for sarcoplasmic reticulum Ca2+-ATPase activation by its substrate and a synthetic allosteric modulator.
Evolution of hierarchy and irreversibility in theoretical cell differentiation model
Authors: Nakamura Yoshiyuki T , Himeoka Yusuke , Saito Nen , Furusawa Chikara
Published: December 2023

The process of cell differentiation in multicellular organisms is characterized by hierarchy and irreversibility in many cases. However, the conditions and selection pressures that give rise to these characteristics remain poorly understood. By using a mathematical model, here we show that the network of differentiation potency (differentiation diagram) becomes necessarily hierarchical and irreversible by increasing the number of terminally differentiated states under certain conditions. The mechanisms generating these characteristics are clarified using geometry in the cell state space. The results demonstrate that the hierarchical organization and irreversibility can manifest independently of direct selection pressures associated with these characteristics, instead they appear to evolve as byproducts of selective forces favoring a diversity of differentiated cell types. The study also provides a new perspective on the structure of gene regulatory networks that produce hierarchical and irreversible differentiation diagrams. These results indicate some constraints on cell differentiation, which are expected to provide a starting point for theoretical discussion of the implicit limits and directions of evolution in multicellular organisms.
Utilizing a cell-free protein synthesis platform for the biosynthesis of a natural product, caffeine
Authors: Ditzel Alexander , Zhao Fanglong , Gao Xue , Phillips George N
Published: December 2023

Natural products are a valuable source of pharmaceuticals, providing a majority of the small-molecule drugs in use today. However, their production through organic synthesis or in heterologous hosts can be difficult and time-consuming. Therefore, to allow for easier screening and production of natural products, we demonstrated the use of a cell-free protein synthesis system to partially assemble natural products in vitro using S-Adenosyl Methionine (SAM)-dependent methyltransferase enzyme reactions. The tea caffeine synthase, TCS1, was utilized to synthesize caffeine within a cell-free protein synthesis system. Cell-free systems also provide the benefit of allowing the use of substrates that would normally be toxic in a cellular environment to synthesize novel products. However, TCS1 is unable to utilize a compound like S-adenosyl ethionine as a cofactor to create ethylated caffeine analogs. The automation and reduced metabolic engineering requirements of cell-free protein synthesis systems, in combination with other synthesis methods, may enable the more efficient generation of new compounds.

Graphical Abstract
Characterization of T-Helper Immune Phenotype in Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) Endorses a Delayed-Type Hypersensitivity Reaction
Authors: Chaudet Kristine M. , Russell-Goldman Eleanor , Horn Thomas D. , Schuler Amy M. , Chan May P. , Nazarian Rosalynn M.
Published: December 2023

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug eruption with a characteristic distribution of erythema on the gluteal/inguinal region and intertriginous areas with unclear pathogenesis. In this study, we aimed to characterize the T-helper immune phenotype in SDRIFE in comparison with psoriasis and eczema to further the understanding of the pathophysiology and immune response of this rare disorder. Immunohistochemical staining was performed on 9 skin biopsies each from SDRIFE, psoriasis, and eczema using immunohistochemistry for CD3 and dual CD4/T-bet, CD4/GATA3, and CD4/RORC to quantify the percentage of Th1, Th2, and Th17 cells, respectively. A significant difference was detected in the average percentage of Th1 between all 3 groups with the highest percentage of Th1 cells seen in psoriasis, followed by SDRIFE and eczema. SDRIFE showed significantly lower Th2 expression as compared to both psoriasis and eczema. There was a trend towards a higher average percentage of Th17 in psoriasis and SDRIFE, and the ratio of Th17:Th2 was significantly higher in samples of SDRIFE compared with both eczema and psoriasis. The findings characterize SDRIFE as a Th1 and possibly Th17-driven process, which could inform future therapeutic options and substantiate the model of SDRIFE as a delayed-type hypersensitivity reaction.
Practice Profile of Practicing Plastic Surgeons: A 20-year Review of Plastic Surgery Statistics
Authors: Gutowski Kristof S. , Chwa Emily S. , Weissman Joshua P. , Garg Stuti P. , Simmons Christopher J. , Brandt Keith E. , Gosain Arun K.
Published: December 2023

Background:

Evaluation of practice patterns by American Board of Plastic Surgery (ABPS) diplomates allows for a greater understanding as to how the field is progressing. Understanding evolving procedural trends can give insight into plastic surgeons’ subspecialty focus and influence resident training to prepare them for future practice.

Methods:

American Society of Plastic Surgeons member only projections for aesthetic and reconstructive procedures were reviewed from 1999 to 2018 in 5-year increments to identify shifts in frequency between the beginning (1999–2003) and end (2014–2018) of the timeframe. Tracer utilization for all four ABPS modules were also examined between 2014 and 2018. Descriptive statistics were performed to identify significant changes (P < 0.05) in subspecialty focus and procedure trends.

Results:

Annual procedure incidence between 2014 and 2018 was compared with that between 1999 and 2003. The annual number of procedures more than doubled from 3,244,084 to 6,628,082. Among reconstructive procedures, there was a statistically significant increase in the number of breast reconstruction, breast implant removal, and maxillofacial surgery procedures, and a statistically significant decrease in the number of procedures focused on reconstruction of birth defects, burn injuries, and hand anomalies. In aesthetic surgery, significant increases were seen in the number of augmentation mammoplasty, abdominoplasty, and mastopexy procedures, with significant decreases in the number of blepharoplasty and rhinoplasty procedures.

Conclusions:

Understanding the changing practice patterns of ABPS diplomates is essential to define the direction that our specialty is taking over time, and to guide program directors in plastic surgery on areas of focus for appropriate training of plastic surgeons.
Increased Prevalence of Clostridioides difficile Infection Among Pediatric Oncology Patients: Risk Factors for Infection and Complications
Authors: Murphy Brianna R. , Dailey Garnes Natalie J. , Hwang Hyunsoo , Peterson Christine B. , Garey Kevin W. , Okhuysen Pablo
Published: December 2023

Background:

Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Methods:

To characterize CDI epidemiology, including risk factors and complications among pediatric oncology patients, we retrospectively reviewed charts of patients 1–18 years old treated at a designated cancer center during 2000–2017. We used fluorescence-based polymerase chain reaction to identify ribotypes causing disease at our institution.

Results:

In 11,366 total patients, we identified 207 CDI cases during the study period. CDI prevalence in our pediatric oncology population was 18 cases per 1000 patients. CDI was highest among patients with acute myeloid leukemia, neuroblastoma, and desmoplastic small round cell tumor (105, 66 and 111 cases per 1000 patients, respectively; P < 0.01). Fever, leukocytosis, elevated creatinine and abdominal radiation and fluoroquinolone exposure concurrent with treatment of CDI were associated with complications. Patients with severe CDI experienced increased mortality. Ribotypes previously associated with severe infection were observed infrequently and were not associated with mortality.

Conclusions:

This is the largest study of CDI in pediatric oncology patients to date. The study identifies specific oncologic diagnoses with increased CDI risk and factors predictive of poor outcomes. As CDI treatment guidelines are developed for this population, these data will be useful for risk stratification of patients in need of early, aggressive treatment.
The diagnosis and treatment for primary cardiac angiosarcoma with N-ras gene mutation and MSI-L: A case report and review of the literature
Authors: Sun Jiachun , Wei Tingting , Sun Bo , Su Jingxiang , Liu Hongyan , Wang Dengkui , Li Xinyang
Published: December 2023

Rationale:

Primary cardiac angiosarcomas (PCA) is a rare malignancy with a poor prognosis. Currently, there is no standard treatment protocol for the PCA. We report a case of PCA in a 51-year-old woman.

Patient concerns:

A 51-year-old woman initially presented with unexplained palpitations and chest tightness accompanied by nausea and vomiting, which worsened after activity and improved after rest. After symptomatic treatment, the symptoms improved, and the above symptoms recurred 8 months later.

Diagnoses:

Positron emission tomography-computed tomography revealed multiple lung nodules of varying sizes, some of which exhibited increased glucose metabolism. Furthermore, a soft tissue mass protruding into the pericardial cavity and involving the adjacent right atrium was observed in the right pericardium. The mass exhibited increased glucose metabolism, suggestive of a pericardial tumor with multiple lung metastases. Finally, histopathologic diagnosis of metastatic angiosarcoma was done by computed tomography-guided percutaneous lung and mediastinal biopsy.

Interventions:

The patient was treated with palliative chemotherapy for the primary cardiac angiosarcomas and hematogenous lung metastasis. One cycle later, the result of Next-Generation Sequencing showed that the microsatellite instability status was determined to be low-level. Based on this result, tislelizumab was added to the original chemotherapy regimen.

Outcomes:

Unfortunately, the patient with PCA passed away after only 2 cycles of chemotherapy, and the cause of death remained unknown.

Lessons:

This case report well demonstrates typical imaging findings of a rare cardiac angiosarcomas and emphasizes importance of early investigation for accurate diagnosis and proper management of the cardiac angiosarcomas.
Thromboelastography characteristics in critically ill patients with liver disease
Authors: Bajwa Ramanpreet K. , Kleb Cerise , Faisal Muhammad Salman , Khan Muhammad Zarrar , Khan Afshin , Lyu Ruishen , Angelini Dana , Sims Omar T. , Modaresi Esfeh Jamak
Published: December 2023

Objective

The purpose of this study was to determine how thromboelastography (TEG) parameters differ by various clinical conditions that commonly occur in patients with cirrhosis, including sepsis, acute on chronic liver failure (ACLF), alcohol-associated hepatitis (AAH) and portal vein thrombosis (PVT).

Background

TEG, a whole blood assay, is used to assess several parameters of coagulation and is becoming increasingly used in clinical practice.

Study

This study was a retrospective chart review of 155 patients admitted to the ICU with decompensated cirrhosis from 2017 to 2019.

Results

The R time was significantly shorter in patients when they were septic compared to when they were not and longer in patients with vs. without ACLF grade 3. Alpha angle and maximum amplitude was decreased in patients with severe AAH compared to those without severe AAH; and maximum amplitude was increased in patients with acute PVT compared to those with chronic PVT. R time was positively correlated with Chronic Liver Failure Consortium Organ Failure and Chronic Liver Failure Consortium ACLF scores (rho = 0.22, P = 0.020), while alpha angle and maximum amplitude were negatively correlated with MELD-NA.

Conclusion

Findings suggest TEG parameters vary in several clinical conditions in patients with decompensated cirrhosis who are admitted to the ICU. Prospective research is needed to confirm our findings and to determine how this knowledge can be used to guide clinical practice, as well as blood product transfusions in the setting of bleeding or prior to invasive procedures.
Basal cortisol levels do not predict adrenal responsiveness in acute decompensated cirrhosis
Authors: Wentworth Brian J. , Schliep Matthew , Novicoff Wendy M. , Henry Zachary H. , Siragy Helmy M.
Published: December 2023

Objective

Morning total cortisol (TC) levels have been shown to predict adrenal dysfunction (AD) in the general population, but their utility in cirrhosis is unknown.

Methods

A retrospective cohort study was performed including all noncritically ill patients at our institution between 2011 and 2022 admitted with acute decompensated cirrhosis who underwent standard-dose adrenocorticotropic hormone (ACTH) stimulation testing. Adrenal dysfunction was defined as an increase in TC (delta TC) level <9 µg/dl 60 minutes after ACTH dosing. Spearman correlation was utilized to assess the relationship between binding globulins and cortisol levels. Multivariate regression analysis was performed to determine if basal TC level or common clinical parameters were predictive of AD.

Results

One hundred and nineteen patients were included, with a median model for end-stage liver disease score of 18. Albumin levels did not correlate with basal TC levels (ρ = 0.127; P = 0.169); basal TC did not correlate with delta TC (ρ = 0.050; P = 0.591). The degree of hypoalbuminemia did not alter these relationships. On multivariate regression, only albumin level [odds ratio (OR) = 0.418; 95% confidence interval (CI), 0.196–0.890; P = 0.024] and MELD score (OR, 1.094; 95% CI, 1.019–1.174; P = 0.014) were predictive of AD. Basal TC levels were not predictive of AD (OR = 0.991; 95% CI, 0.903–1.088; P = 0.855) or delta TC (β = 0.000; 95% CI −0.147 to 0.147; P = 0.999).

Conclusion

Baseline TC levels do not predict ACTH stimulation testing response in patients with acute decompensated cirrhosis. Clinicians should avoid utilizing an isolated morning cortisol result as a screening method for AD in this population.
Evaluation of surveillance system changes to improve detection of disseminated gonococcal infections in Virginia, 2018-2021
Authors: Pugsley River A. , Gadju Gracia , Young Kaylah , Rose Cameron , Haugan Nan , Vasiliu Oana
Published: December 2023

Background

Disseminated gonococcal infection (DGI), a complication of untreated gonorrhea, is rarely reported through routine surveillance. We sought to improve local surveillance system capacity to estimate and monitor the incidence of DGI in Virginia.

Methods

We modified surveillance protocols to identify possible DGI cases using information extracted from gonorrhea case reports and performed provider follow-up using standardized case report forms to confirm DGI diagnosis and collect clinical information. Suspect cases included those with a laboratory report indicating sterile site of specimen collection (e.g. blood, synovial fluid) and/or intravenous (IV) treatment. We performed descriptive analyses to summarize characteristics of suspect and confirmed DGIs and estimated incidence.

Results

After piloting protocols in 2018-2019, we identified 405 suspect DGI cases from 29,294 gonorrhea cases reported in 2020-21 (1.4%). We initiated investigations for 298 (73.6%) of the suspect cases, received provider responses for 105 (25.9%), and confirmed 19 (4.7%) DGI cases. Positive laboratory reports from non-mucosal sites were the most reliable predictor of confirmed DGI status, but most were not confirmed as DGI even when provider follow-up was successful. The confirmed and estimated incidence of DGI was 0.06% and 0.22% respectively. Sixteen (84%) of the confirmed cases were over 25 years of age, 3 (16%) were HIV-positive, and approximately half were male and non-Hispanic black. The majority (15, 74%) were hospitalized, and common manifestations included septic arthritis and bacteremia.

Conclusions

We improved surveillance for DGI in Virginia while incurring minor programmatic costs. Additional efforts to improve the completeness and quality of surveillance data for DGI are needed.
Surgical Outcomes of Laparoscopic-assisted Distal Gastrectomy Versus Totally Laparoscopic Distal Gastrectomy Billroth I for Gastric Cancer
Authors: Motamiez Ahmed , Maximous Doaa , Salem Ahmed A.S. , Ahmed Badawy M. , Kong Seong-Ho , Park Do Joong , Lee Hyuk-Joon , Yang Han-Kwang
Published: December 2023

Objective:

The present study aimed to compare intraoperative and postoperative outcomes of laparoscopic-assisted distal gastrectomy versus totally laparoscopic distal gastrectomy (TLDG) Billroth I (BI) for gastric cancer and to assess the impact of the initial introduction phase of TLDG BI anastomosis.

Patients and Methods:

The study analyzed the prospectively collected data of patients who underwent laparoscopic distal gastrectomy BI from 2014 to 2021 at Seoul National University Hospital.

Results:

Among 1116 patients, laparoscopic-assisted distal gastrectomy BI was performed in 566 patients and TLDG BI was performed in 550 patients. The total laparoscopic arm had a faster mean operative time (190 vs 208 min; P < 0.001) and a shorter postoperative hospital stay (7.4 vs 7.9 d; P < 0.001). Local complications were higher in the total laparoscopic group (17.6% vs 9.9%; P = 0.008) during the early introduction phase.

Conclusion:

The total laparoscopic approach for BI reconstruction is safe and effective with faster operative time, shorter hospital stays, and less wound infection, but it may be associated with an increase in postoperative surgical complications and hospital stay in the early introduction phase.
Using Simulation-Based Experiential Learning to Increase Students’ Ability to Analyze Increasingly Complex Global Health Challenges: A Mixed Methods Study
Authors: Khalid Ahmad Firas , George Megan A. , Eggen Clarissa , Sritharan Aaranee , Wali Faiza , Viens A. M.
Published: December 2023

Traditional didactic teaching approaches fall short of adequately supporting diverse student learning styles. Complementing didactic teaching approaches with simulation-based experiential learning has shown promise in bridging the gap between theoretical knowledge and practical application. However, few studies have rigorously examined the outcomes of this approach in global health education and training. This study aims to evaluate the impact of the World Health Organization World Health Assembly Simulation (WHA Sim), a simulation-based experiential learning platform designed to enhance the application of students’ knowledge and skills in practical settings relating to global health governance.

We employed a sequential mixed-method study between September 2022 and July 2023, starting with an anonymous survey among undergraduate students in the Faculty of Health at York University, in order to evaluate self-reported quantitative metrics related to students’ understanding of simulation-based learning prior to the WHA Sim. We also conducted qualitative interviews among participants of the WHA Sim from diverse health disciplines, aiming to capture multi-disciplinary perspectives. Data was analyzed using simple descriptive statistics for the quantitative data and a framework analysis for qualitative data.

Among 39 survey respondents, 18 were interviewed. The WHA Sim bolstered a wide array of skills, including research capabilities, critical analysis, time management, and organizational effectiveness. Participants also reported improvements in effective interpersonal communication, public speaking, networking, and solution-driven dialogues. Interpersonal skills like collaboration and leadership were notably improved. Moreover, the simulation provided an enhanced understanding of complex issues and offered a fertile ground for career preparation, filling existing knowledge gaps more effectively than traditional learning environments.

Findings demonstrate the value of simulation-based experiential learning among undergraduate students, which illustrates how the WHA Sim can serve as an effective learning tool within global health education and training.
Diabetes related emergency department visits among adults during the COVID-19 pandemic – an analysis of data from the New York City syndromic surveillance system
Authors: Zhilkova Anna , Lall Ramona , Mathes Robert , Chamany Shadi , Olson Donald
Published: December 2023

Objective

New York City was an early epicenter of the COVID-19 pandemic. We aim to describe population level epidemiological trends in diabetes related emergency department (ED) visits among adults in New York City, for the period prior to and encompassing the first four waves of the pandemic.

Research Design and Methods

We used data from the New York City ED syndromic surveillance system during December 30, 2018 through May 21, 2022. This system captures all visits from EDs in the city in near-real time. We matched these visits to laboratory confirmed COVID-19 positivity data beginning with February 15, 2020.

Results

Compared to pre-pandemic baseline levels, diabetes related ED visits noticeably increased during the first wave in spring 2020, though this did not necessarily translate to net increases overall during that period. Visits for diabetic ketoacidosis, particularly among adults with type 2 diabetes, sharply increased before returning to pre-pandemic levels, most notably during wave 1 and wave 4 in winter 2021-2022. Trajectories of diabetes-related ED visits differed by diabetes type, age, and sex. Some ED visit trends did not return to pre-pandemic baseline levels.

Conclusions

The COVID-19 pandemic, especially the first wave in the spring of 2020, coincided with a dramatic shift in diabetes related ED utilization in New York City. Our findings highlight the importance of on-going surveillance of health care utilization for chronic diseases during population-level emergencies like pandemics. A robust syndromic surveillance system that includes infectious and non-infectious syndromes is useful to better prepare, mitigate, and respond to population-level events.

Article Highlights

Diabetes related emergency department (ED) visits in New York City increased dramatically with the emergence of the COVID-19 pandemic in spring 2020.

The trajectory of diabetes-related ED visits differed by diabetes type, age, sex, and pandemic wave.

The diabetes complication of diabetic ketoacidosis among adults with type 2 diabetes showed sharp increases in the first and fourth waves of the pandemic, respectively its initial emergence in spring 2020 and the Omicron variant in winter 2021-2022.

Our findings highlight the importance of on-going surveillance of health care utilization for chronic diseases during population-level emergencies like pandemics.

Data from NYC’s syndromic surveillance system showed major increases in #type2diabetes complications (e.g. diabetic ketoacidosis) during #COVID-19 waves 1 and 4 (Omicron) – this tool may be useful for population-level monitoring of chronic disease complications during emergencies
Imputation of structural variants using a multi-ancestry long-read sequencing panel enables identification of disease associations
Authors: Noyvert Boris , Mesut Erzurumluoglu A , Drichel Dmitriy , Omland Steffen , Andlauer Till F M , Mueller Stefanie , Sennels Lau , Becker Christian , Kantorovich Aleksandr , Bartholdy Boris A , Brænne Ingrid , Bolivar-Lopez Julio Cesar , Mistrellides Costas , Belbin Gillian M , Li Jeremiah H , Pickrell Joseph K , Arora Jatin , Hu Yao ,   Boehringer Ingelheim – Global Computational Biology and Digital Sciences, Wood Clive R , Kriegl Jan M , Podduturi Nikhil , Jensen Jan N , Stutzki Jan , Ding Zhihao
Published: December 2023

Advancements in long-read sequencing technology have accelerated the study of large structural variants (SVs). We created a curated, publicly available, multi-ancestry SV imputation panel by long-read sequencing 888 samples from the 1000 Genomes Project. This high-quality panel was used to impute SVs in approximately 500,000 UK Biobank participants. We demonstrated the feasibility of conducting genome-wide SV association studies at biobank scale using 32 disease-relevant phenotypes related to respiratory, cardiometabolic and liver diseases, in addition to 1,463 protein levels. This analysis identified thousands of genome-wide significant SV associations, including hundreds of conditionally independent signals, thereby enabling novel biological insights. Focusing on genetic association studies of lung function as an example, we demonstrate the added value of SVs for prioritising causal genes at gene-rich loci compared to traditional GWAS using only short variants. We envision that future post-GWAS gene-prioritisation workflows will incorporate SV analyses using this SV imputation panel and framework.
Identifying individuals with rare disease variants by inferring shared ancestral haplotypes from SNP array data
Authors: Robertson Erandee , Grinton Bronwyn E , Oliver Karen L , Fearnley Liam G , Hildebrand Michael S , Sadleir Lynette G , Scheffer Ingrid E , Berkovic Samuel F , Bennett Mark F , Bahlo Melanie
Published: December 2023

We describe FoundHaplo, a novel identity-by-descent algorithm designed to identify individuals with known, untyped, disease-causing variants using only SNP array data. FoundHaplo leverages knowledge of shared disease haplotypes for inherited disease-causing variants to identify individuals who share the disease haplotype and are, therefore, likely to carry the rare (MAF<0.01) variant. We performed a simulation study to evaluate the performance of FoundHaplo across 33 known disease-harbouring loci. We demonstrated the ability of FoundHaplo to infer the presence of two rare (MAF<0.01) pathogenic variants,SCN1Bc.363C>G (p.Cys121Trp) andWWOXc.49G>A (p.E17K), which can cause mild dominant and severe recessive epilepsy respectively, in two large cohorts including 1,573 individuals with epilepsy from the Epi25 cohort and 468,481 individuals from the UK Biobank. We demonstrate that FoundHaplo performs substantially better at inferring the presence of these variants than existing genome-wide imputation approaches. FoundHaplo is a valuable, low-cost screening tool that can be applied to search SNP genotyping array data for disease-causing variants with known founder effects based on shared disease haplotypes. FoundHaplo is available athttps://github.com/bahlolab/FoundHaplo.
De novo design of diverse small molecule binders and sensors using Shape Complementary Pseudocycles
Authors: An Linna , Said Meerit , Tran Long , Majumder Sagardip , Goreshnik Inna , Lee Gyu Rie , Juergens David , Dauparas Justas , Anishchenko Ivan , Coventry Brian , Bera Asim K. , Kang Alex , Levine Paul M. , Alvarez Valentina , Pillai Arvind , Norn Christoffer , Feldman David , Zorine Dmitri , Hicks Derrick R. , Li Xinting , Sanchez Mariana Garcia , Vafeados Dionne K. , Salveson Patrick J. , Vorobieva Anastassia A. , Baker David
Published: December 2023

A general method for designing proteins to bind and sense any small molecule of interest would be widely useful. Due to the small number of atoms to interact with, binding to small molecules with high affinity requires highly shape complementary pockets, and transducing binding events into signals is challenging. Here we describe an integrated deep learning and energy based approach for designing high shape complementarity binders to small molecules that are poised for downstream sensing applications. We employ deep learning generated psuedocycles with repeating structural units surrounding central pockets; depending on the geometry of the structural unit and repeat number, these pockets span wide ranges of sizes and shapes. For a small molecule target of interest, we extensively sample high shape complementarity pseudocycles to generate large numbers of customized potential binding pockets; the ligand binding poses and the interacting interfaces are then optimized for high affinity binding. We computationally design binders to four diverse molecules, including for the first time polar flexible molecules such as methotrexate and thyroxine, which are expressed at high levels and have nanomolar affinities straight out of the computer. Co-crystal structures are nearly identical to the design models. Taking advantage of the modular repeating structure of pseudocycles and central location of the binding pockets, we constructed low noise nanopore sensors and chemically induced dimerization systems by splitting the binders into domains which assemble into the original pseudocycle pocket upon target molecule addition.

One Sentence Summary

We use a pseuodocycle-based shape complementarity optimizing approach to design nanomolar binders to diverse ligands, including the flexible and polar methotrexate and thyroxine, that can be directly converted into ligand-gated nanopores and chemically induced dimerization systems.
The promise and peril of comparing fluorescence lifetime in biology revealed by simulations
Authors: Ma Pingchuan , Sternson Scott , Chen Yao
Published: December 2023

Signaling dynamics are crucial in biological systems, and biosensor-based real-time imaging has revolutionized their analysis. Fluorescence lifetime imaging microscopy (FLIM) excels over the widely used fluorescence intensity imaging by allowing the measurement of absolute signal levels, independent of sensor concentration. This capability enables the comparison of signaling dynamics across different animals, body regions, and timeframes. However, FLIM’s advantage can be compromised by factors like autofluorescence in biological experiments. To address this, we introduce FLiSimBA, a flexible computational framework for realisticFluorescenceLifetimeSimulation forBiologicalApplications. Through simulations, we analyze the signal-to-noise ratios of fluorescence lifetime data, determining measurement uncertainty and providing necessary error bars for lifetime measurements. Furthermore, we challenge the belief that fluorescence lifetime is unaffected by sensor expression and establish quantitative limits to this insensitivity in biological applications. Additionally, we propose innovations, notably multiplexed dynamic imaging that combines fluorescence intensity and lifetime measurements. This innovation can transform the number of signals that can be simultaneously monitored, thereby enabling a systems approach in studying signaling dynamics. Thus, by incorporating diverse factors into our simulation framework, we uncover surprises, identify limitations, and propose advancements for fluorescence lifetime imaging in biology. This quantitative framework supports rigorous experimental design, facilitates accurate data interpretation, and paves the way for technological advancements in fluorescence lifetime imaging.
Hemolymph transfusions transfer heritable learned novel odor preferences to naïve larvae ofBicyclus anynanabutterflies
Authors: Gowri V. , Monteiro Antónia
Published: December 2023

The mechanisms whereby environmental experiences of parents are transmitted to their offspring to impact their behavior and fitness are poorly understood. Previously, we showed that naïveBicyclus anynanabutterfly larvae, whose parents fed on a normal plant feed but coated with a novel odor, inherited a learned preference towards that odor, which had initially elicited avoidance in the naïve parents. Here, we performed simple hemolymph transfusions from odor-fed and control-fed larvae to naïve larval recipients. We found that larvae injected with hemolymph from odor-fed donors stopped avoiding the novel odor, and their naïve offspring preferred the odor more, compared to the offspring of larvae injected with control hemolymph. These results indicate that factors in the hemolymph, potentially the odor molecule itself, play an important role in odor learning and preference transmission across generations. Furthermore, this mechanism of odor preference inheritance, mediated by the hemolymph, bypasses the peripheral odor-sensing mechanisms taking place in the antennae, mouthparts, or legs, and may mediate host plant switching and diversification in the Lepidoptera or more broadly across insects.
e- Health for Fighting Digital Addiction: a Literature Review
Authors: Nurrahima Artika , Pandin Moses Glorino Rumambo , Yusuf Ah.
Published: December 2023

Background

The internet highly used worldwide triggers addiction to technology at various age stages. Digital addiction has various negative impacts on health, social, economic, and educational aspects. Various recent studies explained the influence of technology-based interventions to prevent and overcome digital addiction, which indirectly reduced the negative impact of addiction. The purpose of this study was to analyze the use of e-health in various age ranges, the type of e-health used and the type of intervention that uses e-health as a media for fighting digital addiction.

Method

This study is a literature review related to e-health intervention in digital addiction obtained from data bases: SpringerLink, ScienceDirect, ProQues, Ebsco CINAHL, and Google scholar with keywords and booleans: “internet addiction” OR “smartphone addiction” OR “game addiction” AND therapy OR intervention AND “e-health” OR “digital health” OR “digital intervention” OR “digital education. Articles in this review are limited to English articles from 2020-2023. The PRISMA guidline is used as a reference protocol and evaluation of literature review.

Result

Based on the 11 articles included in this review, e-health interventions are used as strategy to prevent and treat digital addiction in children, adolescents and adults. The majority of the population who use e-health are adolescents. The type of e-health used as the main intervention was smartphone apps, while game was used as additional intervention. The majority of interventions that can be delivered through e-health are CBT based, while other interventions are behavior monitoring and nudge based.

Conclusion

E-health intervention can be used as the main and additional intervention to prevent and overcome digital addiction in various ages, especially adolescents, tend to have a high success rate. The development of e-health can be seen as a promising intervention to facilitate healthy digital behavior change.
Automated workflow for the cell cycle analysis of (non-)adherent cells using a machine learning approach
Authors: Hayatigolkhatmi Kourosh , Soriani Chiara , Soda Emanuel , Ceccacci Elena , Menna Oualid El , Peri Sebastiano , Negrelli Ivan , Bertolini Giacomo , Franchi Gian Martino , Carbone Roberta , Minucci Saverio , Rodighiero Simona
Published: December 2023

Understanding the details of the cell cycle at the level of individual cells is critical for both cellular biology and cancer research. While existing methods using specific fluorescent markers have advanced our ability to study the cell cycle in cells that adhere to surfaces, there is a clear gap when it comes to non-adherent cells. In this study, we combine a specialized surface to improve cell attachment, the genetically-encoded FUCCI(CA)2 sensor, an automated image processing and analysis pipeline, and a custom machine-learning algorithm. This combined approach allowed us to precisely measure the duration of different cell cycle phases in non-adherent cells.

Our method provided detailed information from hundreds of cells under different experimental conditions in a fully automated manner. We validated this approach in two different Acute Myeloid Leukemia (AML) cell lines, NB4 and Kasumi-1, which have unique cell cycle characteristics. Additionally, we tested the impact of drugs affecting the cell cycle in NB4 cells. Importantly, our cell cycle analysis system is freely available and has also been validated for use with adherent cells.

In summary, this report introduces a comprehensive, automated method for studying the cell cycle in both adherent and non-adherent cells, offering a valuable tool for cancer research and drug development.
Agarose disk electroporation method forex vivoretinal tissue cultured at the air-liquid interface reveals electrical stimulus-induced cell cycle reentry in retinal cells
Authors: Stone Megan L. , Lee Hannah H. , Levine Edward M.
Published: December 2023

It is advantageous to culture theex vivomurine retina along with many other tissue types at the air-liquid interface. However, gene delivery to these cultures can be challenging. Electroporation is a fast and robust method of gene delivery, but typically requires submergence in a liquid buffer to allow electric current flow. We have developed a submergence-free electroporation technique using that allows for efficient gene delivery to theex vivomurine retina. This method advances our ability to useex vivoretinal tissue for genetic studies and can easily be adapted for any tissue cultured at an air-liquid interface. Use of this method has revealed valuable insights on the state ofex vivoretinal tissues and the effects of electrical stimulation on retinal cells.

Motivation

Tissues cultured at the air-liquid interface, such as retinal tissue, are adhered to a filter membrane with media underneath but not fully submerged. If tissues are fully submerged in liquid, they detach from the membrane and become damaged. Electroporation typically requires tissue submergence for electric current flow. We have developed a submergence-free electroporation method using an agarose disk for electric current delivery that can efficiently and consistently electroporateex vivoretinal tissue cultured at an air-liquid interface without the need to submerge the tissue and disrupt the culture system.
CUL-6/cullin ubiquitin ligase-mediated degradation of HSP-90 by intestinal lysosomes promotes thermotolerance
Authors: Sarmiento Mario Bardan , Gang Spencer S. , van Oosten-Hawle Patricija , Troemel Emily R.
Published: December 2023

Heat shock can be a lethal stressor. Previously, we described a CUL-6/cullin-ring ubiquitin ligase complex in the nematodeCaenorhabditis elegansthat is induced by intracellular intestinal infection and proteotoxic stress, and that promotes improved survival upon heat shock (thermotolerance). Here, we show that CUL-6 promotes thermotolerance by targeting the heat shock protein HSP-90 for degradation. We show that CUL-6-mediated lowering of HSP-90 protein levels, specifically in the intestine, provides a thermotolerance benefit independent of heat shock factor HSF-1. Furthermore, we show that lysosomal function is required for CUL-6-mediated promotion of thermotolerance and that CUL-6 directs HSP-90 to lysosome-related organelles upon heat shock. Altogether, these results indicate that a CUL-6 ubiquitin ligase promotes organismal survival upon heat shock by promoting HSP-90 degradation in intestinal lysosomes. Thus, HSP-90, a protein commonly associated with protection against heat shock and promoting degradation of other proteins, is actually itself degraded to protect against heat shock.
Identification of a Novel Ferroptosis Inducer with Dual Modulatory Effects on GPX4 Activity and Stability
Authors: Wang Jun , Liao Long , Yang Bo , Miao Beiping , Li Botai , Ma Xuhui , Fitz Annika , Wu Shanshan , He Jia , Zhang Qianqian , Ji Shuyi , Jin Guangzhi , Zhang Jianming , Bernards René , Qin Wenxin , Sun Chong , Wang Cun
Published: December 2023

Ferroptosis is a unique form of intracellular iron-dependent cell death that differs from apoptosis, necrosis, and autophagy. GPX4, an antioxidant defense enzyme, plays a pivotal role as regulator of ferroptosis. Extensive researches suggest that targeting GPX4 holds promise for cancer therapy. However, the current GPX4 inhibitors face challenges due to unfavorable drug-like properties, which hinder their progress in clinical development. In this study, we identified a novel inhibitor called MI-2, demonstrating potent ferroptosis-inducing capacity. Mechanistically, MI-2 effectively inhibits the activity of GPX4 by direct interaction. Furthermore, MI-2 promotes the degradation of GPX4 through its well-established target, MALT1. In multiple cancer models, MI-2 has demonstrated synergistic effects when combined with sorafenib or regorafenib, resulting in enhanced ferroptosis induction. These findings highlight the dual modulatory effects of MI-2 on GPX4 activity and stability, offering a promising starting point for the development of drug-like GPX4 inhibitors with translational potential.