bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of water-cooled cylindrical blanket in JA DEMO
Authors: Youji Someya , Hiroyasu Tanigawa , Yoshiteru Sakamoto ,   the Joint Special Design Team for Fusion DEMO
Published: February 2024

The concept of the tritium breeding blanket for Japan’s DEMOnstration fusion reactor (JA DEMO) has been developed with pressure tightness against in-box loss-of-coolant accidents based on a water-cooled solid breeder concept. The cooling conditions are designed on the pressurized-water reactor water conditions which are the coolant temperature of 290 °C–325 °C and the operating pressure of 15.5 MPa, respectively. The point of the blanket design is to reduce the amount of structural material in casing as well as to ensure its pressure tightness. This is because a decrease in the amount of structural material improves tritium breeding ratio (TBR). A cylindrical structure, a thin wall casing structure which ensures pressure tightness and could increase TBR, is feasible. However, a relatively larger useless space is expected between modules when the cylindrical blanket modules are arranged in a vacuum vessel, which could decrease TBR. Therefore, the cylindrical blanket modules are to be in a close-packed arrangement to reduce useless space. The Be12Ti block (which shows a minor swelling compared to Be) is selected to achieve the target TBR as the net Be density is equivalent to the case of the Be pebble. The use of Be12Ti blocks can reduce or remove the cooling piping inside the module as the Be12Ti block has a higher thermal conductivity than pebbles. As a result of the neutronics, finite element method, and computational fluid dynamics analyses, it was found that the target TBR value can be achieved in cylindrical structure blanket that ensure pressure tightness.
Airbag injuries of the hand: a case-series and literature review
Authors: Mahmoud Asmaa Z B , Alhusain Abdullah M , Alkhadhrawi Mohammed N H , Vasilescu Dana C
Published: February 2024

Motor vehicle accidents are a significant cause of morbidity and mortality worldwide. Airbags aim to reduce the severity of motor vehicle accidents, but their deployment is not without risks. This study presents five cases presenting with diverse forms of upper extremity injuries following airbag deployment. The presented cases highlight the variety of clinical presentations, the differences in diagnostics in terms of imaging modalities, as well as the spectrum of possible outcomes from complete healing to decreased range of motion to persistent neurological symptoms. Understanding the mechanisms and presentations of such injuries can only help in improving and creating new strategies for the prevention of such injuries, as well as their management.
Assessment and Recommendations for Website Platforms of Neuroanesthesiology Fellowship Programs
Authors: Zhitny Vladislav P. , Do Kenny , Kawana Eric , Do Jenifer , Wajda Michael C. , Gallegos Jose , Carey Kyle , Yee Geoff , Hollifield Lauren C. , Montes Arturo , Walton Edward , Ahmed Shah
Published: February 2024

Background:

Websites serve as recruitment and educational tools for many fellowship programs, including neuroanesthesiology. Since the COVID-19 pandemic, when interviews, conferences, and institutional visits were moved online, websites have become more important for applicants when deciding on their preferred fellowship program. This study evaluated the content of the websites of neuroanesthesiology fellowship programs.

Methods:

Neuroanesthesiology fellowship program websites were identified from the websites of the International Council on Perioperative Neuroscience Training and the Society for Neuroscience in Anesthesiology and Critical Care. The content was assessed against 24 predefined criteria.

Results:

Fifty-three fellowship programs were identified, of which 42 websites were accessible through a Google search and available for evaluation. The mean number of criteria met by the 42 fellowship websites was 12/24 (50%), with a range of 6 to 18 criteria. None of the evaluated fellowship websites met all 24 predefined criteria; 20 included more than 50% of the criteria, whereas 7 included fewer than 30% of the criteria. Having a functional website, accessibility through a single click from Google, and a detailed description of the fellowship program were the features of most websites. Information about salary and life in the area, concise program summaries, and biographical information of past and current fellows were missing from a majority of websites.

Conclusion:

Important information was missing from most of the 42 evaluated neuroanesthesiology fellowship program websites, potentially hindering applicants from making informed choices about their career plans.
The Use of Silver Oxynitrate Wound Dressings in the Treatment of Chronic Wounds: A Feasibility Pilot Study
Authors: Rodriguez-Arguello Jimena , Lienhard Karin , De Grood Jill , Geransar Rose , Somayaji Ranjani , Khan Daniyal , Conly John , Ho Chester , Parsons Laurie
Published: February 2024

OBJECTIVE

To evaluate the feasibility and effectiveness of a silver oxynitrate (Ag7NO11) dressing on wound healing in patients with stalled chronic wounds.

METHODS

A prospective pilot study was conducted to determine the feasibility and effect of using silver oxynitrate dressings within an outpatient setting in Alberta, Canada. A total of 23 patients (12 women and 11 men; mean age, 66.1 ± 13.8 years) with a chronic wound that failed to heal with conventional treatment were included in the study. Wound assessments including the Bates-Jensen Wound Assessment Tool, wound-related pain, wound size, and patient quality of life (QoL) were conducted at baseline, after dressing application for 1 and 2 weeks, and during 4- and 12-week follow-ups.

RESULTS

Dressing application at 1 and 2 weeks improved patients’ wound healing progression as measured through significantly decreased Bates-Jensen Wound Assessment Tool scores with a more than 10% decrease at 4- and 12-week follow-up (P < .001). Pain (P = .004), and QoL psyche subscore (P = .008) significantly improved at 4-week follow-ups, although wound area, perimeter, and QoL body and everyday subscores were not significantly affected. Wound size was not significantly affected.

CONCLUSIONS

The silver oxynitrate dressing may improve healing progression in patients with chronic wounds, enhance patient experience by reducing wound-related pain, and improve patients’ mental well-being. Further studies are warranted to elucidate the effect of silver oxynitrate dressings on wound area, perimeter, and volume measurements.
Various Therapies for Lymphedema and Chronic Venous Insufficiency, Including a Multimodal At-Home Nonpneumatic Compression Treatment
Authors: Barnhart Heather , Maldonado Thomas , Rockson Stanley G.
Published: February 2024

Lymphedema and chronic venous insufficiency (CVI) affect millions of people and require lifelong management. Many compression options exist for the long-term management of these conditions; however, limitations in patient mobility and adherence are common. Current options for care often present challenges with adherence because they are time-intensive and cumbersome. Innovation is needed to improve compression options for patients with chronic edematous conditions, particularly because lymphedema and CVI benefit from combination interventions. In this narrative review, the authors focus on long-term management strategies for lymphedema and CVI and highlight a nonpneumatic compression device designed for ease of use in the management of lymphedema and CVI. Using a nonpneumatic compression device that combines multiple treatment modalities demonstrates improved efficacy, quality of life, and patient adherence.
Association Between Hearing Loss, Asymmetric Hearing, and Postural Instability
Authors: Wang Yang , Zhong Mei , Li Yifan , Liu Yehai , Tong Busheng , Qiu Jianxin , Chen Shanwen
Published: February 2024

Objectives:

Recent studies have suggested that older adults with hearing loss (HL) are at a greater risk of postural instability than those with normal hearing. However, little is known regarding this association in middle-aged individuals. The relationships between HL laterality, asymmetric hearing, and posture control are similarly unclear. The purpose of this study was to investigate the effects of hearing status on postural control and to explore the dose-response relationship between the hearing threshold and postural instability risk in middle-aged adults.

Design:

This cross-sectional study included 1308 participants aged 40 to 69 years with complete audiometric and standing balance function data from the 2001–2004 National Health and Nutrition Examination Survey. Speech-frequency HL was defined as a pure-tone average at 0.5, 1, 2, and 4 kHz of >25 dB in the better-hearing ear; high-frequency HL was defined as a pure-tone average at 3, 4, and 6 kHz of >25 dB. Asymmetric hearing was defined as a difference in the pure-tone average >15 dB between ears. Postural instability was defined as participants ending the modified Romberg test in condition 4.

Results:

After adjustment for sociodemographic variables, lifestyle, and comorbidities, speech-frequency HL, except for unilateral HL, was associated with increased postural instability (mild HL: odds ratio [OR], 2.33; 95% confidence interval [CI], 1.25–4.35; moderate-to-severe HL: OR, 3.59; 95% CI, 1.61–8.03). Compared with individuals with normal bilateral hearing, participants with bilateral HL also showed a higher risk of postural instability (OR, 2.88; 95% CI, 1.61–5.14). The OR for postural instability among participants with asymmetric hearing compared with those with symmetric hearing was 2.75 (95% CI, 1.37–5.52). Furthermore, each 10 dB increase in the speech-frequency hearing threshold was associated with a 44% higher risk of postural instability.

Conclusions:

Hearing loss is associated with poorer postural control. Individuals with asymmetric hearing have a higher postural instability risk compared with those with symmetric hearing. Further studies are needed to confirm these findings and the causality. Moreover, future studies are warranted to assess whether hearing aids are beneficial for the restoration of impaired balance functions.
A Personalized Cell-Based Therapy for Ischemic Heart Failure With Reduced Ejection Fraction: Safety and Feasibility Outcomes of the Roll-In Cohort of the CardiAMP Cell Therapy Trial and Review of Similar Trials
Authors: Feldman Jared M. , Frishman William H. , Aronow Wilbert S.
Published: February 2024

CardiAMP Cell Therapy for Heart Failure trial is a prospective, multicenter, randomized, controlled, double-blinded trial that has been granted breakthrough designation by the United States Food and Drug Administration. This trial evaluates clinical outcomes of intramyocardial delivery of a high dose of autologous bone marrow mononuclear cells in chronic postmyocardial infarction heart failure patients. This trial represents the first attempt to personalize marrow-derived cell-based therapy for the treatment of ischemic heart failure with reduced ejection fraction. The roll-in cohort of 10 patients demonstrated improvements in 6-minute walk distance at 6 months (+47.8 m, P = 0.01), 12 months (+46.4 m, P = 0.06), and 24 months (+31 m), and improvements in New York Heart Association class at 3 months (P = 0.015) and 6 months (P = 0.037). Four patients were reduced to New York Heart Association class I at 24 months and Minnesota Living with Heart Failure Questionnaire score was improved in 6 of 10 patients at 24 months. The improved clinical outcomes demonstrated in CardiAMP are consistent with previous clinical trials including the Transendocardial Autologous Cells in Ischemic Heart Failure (TAC-HFT) trial, Prospective Randomized Trial of Direct Endomyocardial Implantation of Bone Marrow Cells for Treatment of Severe Coronary Artery Diseases (PROTECT-CAD), and REGENERATE-Ischemic Heart Disease trial.
A Rare Case of Varicella Zoster Infection in Hemorrhoids in a Patient With Inflammatory Bowel Disease
Authors: Siatecka Hanna , Al-Awami Sarah , Siddiqi Ahsan , Diwan A. Hafeez
Published: February 2024

Hemorrhoids are normal anatomical structures in the anus. When symptomatic, they prompt medical attention due to pain, rectal bleeding, and discomfort. Treatment includes dietary modifications, rubber band ligations, sclerotherapy, cryotherapy, or hemorrhoidectomy. Histologic examination is important to rule out incidental findings, such as perianal intraepithelial neoplasia, anal carcinoma, melanoma, or coexisting infections. Special attention should be given when patient is immunocompromised. We present a case of a 41-year-old man with a history of ulcerative colitis on adalimumab who presented with anal lesions. He was diagnosed with hemorrhoids and surgically treated. Microscopic examination confirmed the diagnosis of hemorrhoids. However, foci of epithelium with viral cytopathic effects were noted. A varicella zoster virus (VZV)-specific immunostain was positive in the areas of interest confirming the diagnosis of the VZV infection limited to the hemorrhoids. Combined herpes simplex virus type 1 and 2 (HSV 1 and HSV 2) immunostain was also performed and was negative. Anal herpes has been widely described in the literature, particularly in immunocompromised patients. However, isolated VZV infection in hemorrhoids to the best of our knowledge has never been reported.
Cutaneous Malignant Mixed Tumor With Pulmonary Metastasis: A Case Report and Literature Review
Authors: Haberecht Hannah , Tekin Burak , Warren Krista , Guo Ruifeng (Ray)
Published: February 2024

Background:

Cutaneous malignant mixed tumor (MMT) is a rare sweat gland–derived tumor characterized by admixed malignant epithelial cells and chondromyxoid stroma. Approximately 50 cases have been described in the literature. Metastasis, which may occur in more than one-third of cases, is most common in the lung.

Methods:

We summarized the clinicopathologic features of a patient with cutaneous MMT metastatic to the lungs. A literature review of similar cases was completed using Web of Science, Scopus, and PubMed databases.

Results:

A woman in her 70s presented with an enlarging mass on her left eyebrow; histopathologic examination showed large islands of atypical cells with increased mitotic activity, admixed with necrosis on a background of fibrotic and chondromyxoid stroma. Multiple lung nodules were identified during follow-up. Examination of a pulmonary core needle biopsy specimen was consistent with metastatic cutaneous MMT. Literature review identified 10 cases published between 1980 and 2017. Most primary tumors were large (≥4 cm). Local recurrence was uncommon, and the lung was the only metastatic site in 5 cases. Histopathologically, metastatic tumors were described as more cellular, with diminished stromal tissue compared with the primary lesion.

Conclusion:

This is 1 of the 11 reports of cutaneous MMT with metastasis to the lungs found in the English-language literature published after 1980. Of note, most reports were published before 1990, making this case study one of the few contemporary descriptions of cutaneous MMT with pulmonary metastases. We think that the present case report will increase the awareness of this rare tumor.
Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes
Authors: Ufere Nneka N. , Serper Marina , Kaplan Alyson , Horick Nora , Indriolo Teresa , Li Lucinda , Satapathy Nishant , Donlan John , Castano Jimenez Janeth C. , Lago-Hernandez Carlos , Lieber Sarah , Gonzalez Carolina , Keegan Eileen , Schoener Kimberly , Bethea Emily , Dageforde Leigh-Anne , Yeh Heidi , El-Jawahri Areej , Park Elyse R. , Vodkin Irine , Schonfeld Emily , Nipp Ryan , Desai Archita , Lai Jennifer C.
Published: February 2024

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p=0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85–8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61–16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p=0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p<0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.
COVID-19 vaccine-induced liver injury
Authors: Shroff Hersh
Published: February 2024

Purpose of review

The rapid rollout and uptake of novel coronavirus disease 2019 (COVID-19) vaccines has been accompanied by a small yet noticeable accumulation of reports of liver injury occurring after vaccination. This review describes the present evidence surrounding COVID-19 vaccine-induced liver injury (VILI).

Recent findings

Liver injury occurring after the COVID-19 vaccine often presents clinically similar to autoimmune hepatitis, with positive autoantibodies and a portal and lobular inflammatory infiltrate and varying degrees of necrosis on biopsy. The overwhelming majority of patients recover, often spontaneously or with a limited course of immunosuppression. The overall incidence of this phenomenon appears to be exceedingly low.

Providers should remain vigilant for ongoing reports of VILI after COVID-19 and yet feel reassured by the low incidence and high likelihood of recovery. Ongoing genetic and histological study, as well as longer-term follow-up of presently identified cases, will shed further light on the clinical entity of VILI.
Terlipressin for hepatorenal syndrome
Authors: Wong Florence
Published: February 2024

Purpose of review

The definition and diagnostic criteria of hepatorenal syndrome-acute kidney injury (HRS-AKI) has undergone recent changes. A major vasoconstrictor, terlipressin, has recently been approved as pharmacotherapy for HRS-AKI in the United States. The purpose of this review is to familiarize the readers with these new diagnostic criteria of HRS-AKI, and how best to use terlipressin.

Recent findings

Terlipressin is effective either as bolus dosing or continuous infusion and can achieve reversal of HRS-AKI in approximately 40% of patients. Continuous infusion allows lower daily dose with equal efficacy and less side effects but not an approved mode of administration in the United States. Response to terlipressin in the randomized controlled trials was defined as repeat reduction of serum creatinine to less than 1.5 mg/dl. Newer studies will likely require response to treatment to be defined as a repeat serum creatinine to be less than 0.3 mg/dl from baseline. Terlipressin use is associated with ischemic side effects and potential for respiratory failure development.

Careful patient selection and close monitoring are necessary for its use. Response to terlipressin with HRS-AKI reversal is associated with improved outcomes with better survival and less requirement for renal replacement therapy.
Epidemiology and Clinical Characteristics of Pediatric Sepsis in PICUs in Southwest China: A Prospective Multicenter Study*
Authors: Liu Rong , Yu Zhicai , Xiao Changxue , Xu Feng , Xiao Shufang , He Juan , Shi Yan , Hua Yuanyuan , Zhou Jimin , Zhang Guoying , Wang Tao , Jiang Jianyu , Xiong Daoxue , Chen Yan , Xu Hongbo , Yun Hong , Sun Hui , Pan Tingting , Wang Rui , Zhu Shuangmei , Huang Dong , Liu Yujiang , Hu Yuhang , Ren Xinrui , Shi Mingfang , Song Sizun , Luo Jumei , He Gang , Zhang Juan
Published: February 2024

OBJECTIVES:

To describe the epidemiological characteristics of pediatric sepsis in Southwest China PICUs.

DESIGN:

A prospective, multicenter, and observational study.

SETTING:

Twelve PICUs in Southwest China.

PATIENTS:

The patients admitted to the PICU from April 1, 2022, to March 31, 2023. The age ranged from 28 days to 18 years. All patients met the criteria of severe sepsis or septic shock.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of the 31 PICUs invited to participate, 12 PICUs (capacity of 292 beds) enrolled patients in the study. During the study period, 11,238 children were admitted to the participating PICUs, 367 (3.3%) of whom met the diagnosis of severe sepsis or septic shock. The most prevalent sites of infection were the respiratory system (55%) and the digestive system (15%). The primary treatments administered to these patients included antibiotics (100%), albumin (61.3%), invasive mechanical ventilation (58.7%), glucocorticoids (55.6%), blood products (51%), gammaglobulin (51%), and vasoactive medications (46.6%). Sepsis-related mortality in the PICU was 11.2% (41/367). Nearly half of the sepsis deaths occurred within the first 3 days of PICU admission (22/41, 53.7%). The mortality rate of septic shock (32/167, 19.2%) was significantly higher than that of severe sepsis (9/200, 4.5%;p< 0.001). The outcomes of a multivariate logistic regression analysis suggested that a higher pediatric Sequential Organ Failure Assessment score, and the use of invasive mechanical ventilation and vasoactive medications were independently associated with PICU mortality in children with sepsis.

CONCLUSIONS:

This report updates the epidemiological data of pediatric sepsis in PICUs in Southwest China. Sepsis is still a life-threatening disease in children.
Expansion formulae for flexural-gravity wave propagation during wave blocking
Authors: Chandra Barman Sunil , Chanda Ayan
Published: February 2024

Flexural-gravity wave blocking occurs in the presence of lateral compressive force. The existing expansion formulae for the velocity potential were limited in the case of distinct real roots of the dispersion relation with the multiplicity one. This limitation is overcome, and we obtain the complete solution for the flexural-gravity wave-maker problem at blocking and saddle points by deriving the expansion formula for velocity potential using the Fourier transform corresponding to the roots of the dispersion relation with multiplicity two and three, respectively. Further, we check the convergence of the newly derived expansion formulae by using the spectral representation of the associated eigenfunction. It has been proved that the eigenfunctions related to the expansion formulae are linearly dependent and satisfy the orthogonal mode-coupling relation. Next, we solve a model problem of flexural-gravity wave scattering by a crack using the derived expansion formulae and establish the energy balance relation by applying Green’s integral theorem at blocking points for infinite water depth. In addition, we have presented the validation of energy balance relation involving the generalized scattering coefficients.
Demographic feedbacks during evolutionary rescue can slow or speed adaptive evolution
Authors: Draghi Jeremy A. , McGlothlin Joel W. , Kindsvater Holly K.
Published: February 2024

Populations declining toward extinction can persist via genetic adaptation in a process called evolutionary rescue. Predicting evolutionary rescue has applications ranging from conservation biology to medicine, but requires understanding and integrating the multiple effects of a stressful environmental change on population processes. Here we derive a simple expression for how generation time, a key determinant of the rate of evolution, varies with population size during evolutionary rescue. Change in generation time is quantitatively predicted by comparing how intraspecific competition and the source of maladaptation each affect the rates of births and deaths in the population. Depending on the difference between two parameters quantifying these effects, the model predicts that populations may experience substantial changes in their rate of adaptation in both positive and negative directions, or adapt consistently despite severe stress. These predictions were then tested by comparison to the results of individual-based simulations of evolutionary rescue, which validated that the tolerable rate of environmental change varied considerably as described by analytical results. We discuss how these results inform efforts to understand wildlife disease and adaptation to climate change, evolution in managed populations and treatment resistance in pathogens.
Public perceptions of trophy hunting are pragmatic, not dogmatic
Authors: Hare Darragh , Dickman Amy J. , Johnson Paul J. , Rono Betty J. , Mutinhima Yolanda , Sutherland Chris , Kulunge Salum , Sibanda Lovemore , Mandoloma Lessah , Kimaili David
Published: February 2024

Fierce international debates rage over whether trophy hunting is socially acceptable, especially when people from the Global North hunt well-known animals in sub-Saharan Africa. We used an online vignette experiment to investigate public perceptions of the acceptability of trophy hunting in sub-Saharan Africa among people who live in urban areas of the USA, UK and South Africa. Acceptability depended on specific attributes of different hunts as well as participants' characteristics. Zebra hunts were more acceptable than elephant hunts, hunts that would provide meat to local people were more acceptable than hunts in which meat would be left for wildlife, and hunts in which revenues would support wildlife conservation were more acceptable than hunts in which revenues would support either economic development or hunting enterprises. Acceptability was generally lower among participants from the UK and those who more strongly identified as an animal protectionist, but higher among participants with more formal education, who more strongly identified as a hunter, or who would more strongly prioritize people over wild animals. Overall, acceptability was higher when hunts would produce tangible benefits for local people, suggesting that members of three urban publics adopt more pragmatic positions than are typically evident in polarized international debates.
Different photoperiodic responses in diapause induction can promote the maintenance of genetic diversity via the storage effect in
Daphnia pulex
Authors: Otake Yurie , Yamamichi Masato , Hirata Yuka , Odagiri Haruka , Yoshida Takehito
Published: February 2024

Understanding mechanisms that promote the maintenance of biodiversity (genetic and species diversity) has been a central topic in evolution and ecology. Previous studies have revealed that diapause can contribute to coexistence of competing genotypes or species in fluctuating environments via the storage effect. However, they tended to focus on differences in reproductive success (e.g. seed yield) and diapause termination (e.g. germination) timing. Here we tested whether different photoperiodic responses in diapause induction can promote coexistence of two parthenogenetic (asexual) genotypes of
Daphnia pulex
in Lake Fukami-ike, Japan. Through laboratory experiments, we confirmed that short day length and low food availability induced the production of diapausing eggs. Furthermore, we found that one genotype tended to produce diapausing eggs in broader environmental conditions than the other. Terminating parthenogenetic reproduction earlier decreases total clonal production, but the early diapausing genotype becomes advantageous by assuring reproduction in ‘short’ years where winter arrival is earlier than usual. Empirically parameterized theoretical analyses suggested that different photoperiodic responses can promote coexistence via the storage effect with fluctuations of the growing season length. Therefore, timing of diapause induction may be as important as diapause termination timing for promoting the maintenance of genetic diversity in fluctuating environments.
Spontaneous playful teasing in four great ape species
Authors: Laumer I. B. , Winkler S. L. , Rossano F. , Cartmill E. A.
Published: February 2024

Joking draws on complex cognitive abilities: understanding social norms, theory of mind, anticipating others' responses and appreciating the violation of others’ expectations. Playful teasing, which is present in preverbal infants, shares many of these cognitive features. There is some evidence that great apes can tease in structurally similar ways, but no systematic study exists. We developed a coding system to identify playful teasing and applied it to video of zoo-housed great apes. All four species engaged in intentionally provocative behaviour, frequently accompanied by characteristics of play. We found playful teasing to be characterized by attention-getting, one-sidedness, response looking, repetition and elaboration/escalation. It takes place mainly in relaxed contexts, has a wide variety of forms, and differs from play in several ways (e.g. asymmetry, low rates of play signals like the playface and absence of movement-final ‘holds’ characteristic of intentional gestures). As playful teasing is present in all extant great ape genera, it is likely that the cognitive prerequisites for joking evolved in the hominoid lineage at least 13 million years ago.
Taking the beat of the Arctic: are lemming population cycles changing due to winter climate?
Authors: Gauthier Gilles , Ehrich Dorothée , Belke-Brea Maria , Domine Florent , Alisauskas Ray , Clark Karin , Ecke Frauke , Eide Nina E. , Framstad Erik , Frandsen Jay , Gilg Olivier , Henttonen Heikki , Hörnfeldt Birger , Kataev Gennadiy D. , Menyushina Irina E. , Oksanen Lauri , Oksanen Tarja , Olofsson Johan , Samelius Gustaf , Sittler Benoit , Smith Paul A. , Sokolov Aleksandr A. , Sokolova Natalia A. , Schmidt Niels M.
Published: February 2024

Reports of fading vole and lemming population cycles and persisting low populations in some parts of the Arctic have raised concerns about the spread of these fundamental changes to tundra food web dynamics. By compiling 24 unique time series of lemming population fluctuations across the circumpolar region, we show that virtually all populations displayed alternating periods of cyclic/non-cyclic fluctuations over the past four decades. Cyclic patterns were detected 55% of the time (
n
= 649 years pooled across sites) with a median periodicity of 3.7 years, and non-cyclic periods were not more frequent in recent years. Overall, there was an indication for a negative effect of warm spells occurring during the snow onset period of the preceding year on lemming abundance. However, winter duration or early winter climatic conditions did not differ on average between cyclic and non-cyclic periods. Analysis of the time series shows that there is presently no Arctic-wide collapse of lemming cycles, even though cycles have been sporadic at most sites during the last decades. Although non-stationary dynamics appears a common feature of lemming populations also in the past, continued warming in early winter may decrease the frequency of periodic irruptions with negative consequences for tundra ecosystems.
Behavioural ecology meets oncology: quantifying the recovery of animal behaviour to a transient exposure to a cancer risk factor
Authors: Klaassen Hiske , Tissot Sophie , Meliani Jordan , Boutry Justine , Miltiadous Anna , Biro Peter A. , Mitchell David J. , Ujvari Beata , Schultz Aaron , Thomas Frédéric , Dujon Antoine M.
Published: February 2024

Wildlife is increasingly exposed to sublethal transient cancer risk factors, including mutagenic substances, which activates their anti-cancer defences, promotes tumourigenesis, and may negatively impact populations. Little is known about how exposure to cancer risk factors impacts the behaviour of wildlife. Here, we investigated the effects of a sublethal, short-term exposure to a carcinogen at environmentally relevant concentrations on the activity patterns of wildGirardia tigrinaplanaria during a two-phase experiment, consisting of a 7-day exposure to cadmium period followed by a 7-day recovery period. To comprehensively explore the effects of the exposure on activity patterns, we employed the double hierarchical generalized linear model framework which explicitly models residual intraindividual variability in addition to the mean and variance of the population. We found that exposed planaria were less active compared to unexposed individuals and were able to recover to pre-exposure activity levels albeit with a reduced variance in activity at the start of the recovery phase. Planaria showing high activity levels were less predictable with larger daily activity variations and higher residual variance. Thus, the shift in behavioural variability induced by an exposure to a cancer risk factor can be quantified using advanced tools from the field of behavioural ecology. This is required to understand how tumourous processes affect the ecology of species.
Clinical application of whole-genome sequencing for precision oncology of solid tumors
Authors: Kim Ryul , Kim Seokhwi , Oh Brian Baek-Lok , Yu Woo Sik , Kim Chang Woo , Hur Hoon , Son Sang-Yong , Yang Min Jae , Cho Dae Sung , Ha Taeyang , Heo Subin , Jang Jeon Yeob , Yun Jae Sung , Kwack Kyu-Sung , Kim Jai Keun , Huh Jimi , Lim Sun Gyo , Han Sang-Uk , Lee Hyun Woo , Park Ji Eun , Kim Chul-Ho , Roh Jin , Koh Young Wha , Lee Dakeun , Kim Jang-Hee , Lee Gil Ho , Noh Choong-Kyun , Jung Yun Jung , Park Ji Won , Sheen Seungsoo , Ahn Mi Sun , Choi Yong Won , Kim Tae-Hwan , Kang Seok Yun , Choi Jin-Hyuk , Baek Soo Yeon , Lee Kee Myung , Kim Sun Il , Noh Sung Hyun , Kim Se-Hyuk , Hwang Hyemin , Joo Eunjung , Lee Shinjung , Shin Jong-Yeon , Yun Ji-Young , Park Junggil , Yi Kijong , Kwon Youngoh , Lee Won-Chul , Park Hansol , Lim Joonoh , Yi Boram , Koo Jaemo , Koh June-Young , Lee Sangmoon , Lee Yuna , Lee Bo-Rahm , Connolly-Strong Erin , Ju Young Seok , Kwon Minsuk
Published: February 2024

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. While targeted panel sequencing (TPS) has been a key clinical tool over the past decade, advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) with two primary objectives: 1) assessing actionability for therapeutic options, and 2) providing clarity for clinical questions. Of the 120 various solid cancer patients enrolled, 95 (79%) successfully received genomics reports within a median of 11 working days from sampling to report. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability, and 81% (13/16) to clinical clarity. These benefits encompass selection of informed therapeutics and/or active clinical trials with driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and advocate for its integration into routine clinical practice to provide a complete genomic landscape for tailored cancer management.
Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya
Published: February 2024

Identification of accurate biomarkers is still particularly urgent for improving the poor survival of chronic obstructive pulmonary disease (COPD) patients. In this investigation, we aimed to identity the potential biomarkers in COPD via bioinformatics and next generation sequencing (NGS) data analysis. In this investigation, the differentially expressed genes (DEGs) in COPD were identified using NGS dataset (GSE239897) from Gene Expression Omnibus (GEO) database. Subsequently, gene ontology (GO) and pathway enrichment analysis was conducted to evaluate the underlying molecular mechanisms involved in progression of COPD. Protein-protein interaction (PPI), modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were performed to determine the hub genes, miRNAs and TFs. The receiver operating characteristic (ROC) analysis was performed to determine the diagnostic value of hub genes. A total of 956 overlapping DEGs (478 up regulated and 478 down regulated genes) were identified in the NGS dataset. DEGs were mainly associated with GO functional terms and pathways in cellular response to stimulus. response to stimulus, immune system and neutrophil degranulation. There were 10 hub genes (MYC, LMNA, VCAM1, MAPK6, DDX3X, SHMT2, PHGDH, S100A9, FKBP5 and RPS6KA2) identified by PPI, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis. In conclusion, the DEGs, relative GO terms, pathways and hub genes identified in the present investigation might aid in understanding of the molecular mechanisms underlying COPD progression and provide potential molecular targets and biomarkers for COPD.
Probing the Depths for Diagnostic Performance of Biparametric and Multiparametric MRI for Prostate Cancer Detection- A Meta-Analysis
Authors: Desai Dev , Gami Vismit , Shah Abhijay B. , Raval Dwija , Gupta Parth , Shah Hetvi
Published: February 2024

Background

Prostate cancer is a malignancy that originates in the prostate gland,and can vary in aggressiveness, often requiring a combination of diagnostic methods and imaging for accurate detection and management. In an attempt to ensure timely diagnosis and prevent complications, the choice of the right diagnostic modality becomes crucial. MRI has gained prominence in the diagnosis of prostate cancer. MRI aids prostate cancer diagnosis by pinpointing suspicious areas for in-depth investigation and guiding precise biopsies, enhancing accuracy. It also informs treatment plans by visualizing tumour extent and assists in monitoring disease progression during active surveillance. The purpose of this meta-analysis is to ascertain the accuracy of MRI in diagnosing prostate cancer.

Methodology

Medical literature was comprehensively searched and reviewed without restrictions to particular study designs, or publication dates using PubMed, Cochrane Library, and Google Scholar databases for all relevant literature. The extraction of necessary data proceeded after specific inclusion and exclusion criteria were applied. In this Meta-Analysis, A total of 47 RCTs with 13,211 subjects were selected for comparing Multiparametric MRI vs. Gold Standard and A total of 23 RCTs with 3440 subjects were selected for comparing Biparametric MRI vs Gold Standard.

Two writers independently assessed the calibre of each study as well as the use of the Cochrane tool for bias risk apprehension. The statistical software packages RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20), and Excel in Stata 14 were used to perform the statistical analyses.

Results

We calculated the sensitivity and specificity of multiparametric as well as biparametric MRI. The Multiparametric MRI demonstrates a sensitivity of 0.84 (95% confidence interval: 0.83 - 0.85) and specificity of 0.69 (95% confidence interval: 0.68 - 0.70). Meanwhile, Biparametric MRI shows a sensitivity of 0.85 (95% confidence interval: 0.84 - 0.86) and specificity of 0.71 (95% confidence interval: 0.69 - 0.73).

Conclusion

In conclusion, both Multiparametric MRI and Biparametric MRI exhibit high sensitivity values of 0.84 and 0.85, respectively, indicating their ability to accurately detect prostate cancer. MRI is a robust diagnostic tool for prostate cancer due to its high-resolution imaging and multiparametric approach. It enables targeted biopsies, informs treatment plans, and aids in active surveillance.
Time-varying Spatial Propagation of Brain Networks in fMRI data
Authors: Bostami Biozid , Lewis Noah , Agcaoglu Oktay , Turner Jessica A. , van Erp Theo , Ford Judith M , Calhoun Vince , Iraji Armin
Published: February 2024

Spontaneous neural activity coherently relays information across the brain. Several efforts have been made to understand how spontaneous neural activity evolves at the macro-scale level as measured by resting-state functional magnetic resonance imaging (rsfMRI). Previous studies observe the global patterns and flow of information in rsfMRI using methods such as sliding window or temporal lags. However, to our knowledge, no studies have examined spatial propagation patterns evolving with time across multiple overlapping 4D networks. Here, we propose a novel approach to study how dynamic states of the brain networks spatially propagate and evaluate whether these propagating states contain information relevant to mental illness. We implement a lagged windowed correlation approach to capture voxel-wise network-specific spatial propagation patterns in dynamic states. Results show systematic spatial state changes over time, which we confirmed are replicable across multiple scan sessions using human connectome project data. We observe networks varying in propagation speed; for example, the default mode network (DMN) propagates slowly and remains positively correlated to blood oxygenation level-dependent (BOLD) signal for 6-8 seconds, whereas the visual network propagates much quicker. We also show that summaries of network specific propagative patterns are linked to schizophrenia. More specifically, we find significant group differences in multiple dynamic parameters between schizophrenia patients and controls within four large-scale networks: default mode, temporal lobe, subcortical, and visual network. Individuals with schizophrenia spend more time in certain propagating states. In summary, this study introduces a promising general approach to exploring the spatial propagation in dynamic states of brain networks and their associated complexity and reveals novel insights into the neurobiology of schizophrenia.
Cross-species real time detection of trends in pupil size fluctuation
Authors: Kronemer Sharif I. , Gobo Victoria E. , Walsh Catherine R. , Teves Joshua B. , Burk Diana C. , Shahsavarani Somayeh , Gonzalez-Castillo Javier , Bandettini Peter A.
Published: February 2024

Pupillometry is a popular method because pupil size is easily measured, sensitive to central neural activity, and associated with behavior, cognition, emotion, and perception. Currently, there is no method for online monitoring phases of pupil size fluctuation. We introducertPupilPhase– an open source software that automatically detects trends in pupil size in real time, enabling novel implementations of real time pupillometry towards achieving numerous research and translational goals. We validated the performance of rtPupilPhase on human, rodent, and monkey pupil data and propose future applications of real time pupillometry.
Identification of hippocampal area CA2 in hamster and vole brain
Authors: Siegler Preston Nicole , Shaughnessy Emma K. , Horman Brian , Vierling Tia T. , King Darron H. , Patisaul Heather B. , Huhman Kim L. , Alexander Georgia M. , Dudek Serena M.
Published: February 2024

Prairie voles (Microtus ochrogaster) and Syrian, or golden, hamsters (Mesocricetus auratus) are closely related to mice (Mus musculus) and rats (Rattus norvegicus, for example) and are commonly used in studies of social behavior including social interaction, social memory, and aggression. The CA2 region of the hippocampus is known to play a key role in social memory and aggression in mice and responds to social stimuli in rats, likely owing to its high expression of oxytocin and vasopressin 1b receptors. However, CA2 has yet to be identified and characterized in hamsters or voles. In this study, we sought to determine whether CA2 could be identified molecularly in vole and hamster. To do this, we used immunofluorescence with primary antibodies raised against known molecular markers of CA2 in mice and rats to stain hippocampal sections from voles and hamsters in parallel with those from mice. Here, we report that, like in mouse and rat, staining for many CA2 proteins in vole and hamster hippocampus reveals a population of neurons that express regulator of G protein signaling 14 (RGS14), Purkinje cell protein 4 (PCP4) and striatal-enriched protein tyrosine phosphatase (STEP), which together delineate the borders with CA3 and CA1. These cells were located at the distal end of the mossy fiber projections, marked by the presence of Zinc Transporter 3 (ZnT-3) and calbindin in all three species. In addition to staining the mossy fibers, calbindin also labeled a layer of CA1 pyramidal cells in mouse and hamster but not in vole. However, Wolframin ER transmembrane glycoprotein (WFS1) immunofluorescence, which marks all CA1 neurons, was present in all three species and abutted the distal end of CA2, marked by RGS14 immunofluorescence. Staining for two stress hormone receptors—the glucocorticoid (GR) and mineralocorticoid (MR) receptors—was also similar in all three species, with GR staining found primarily in CA1 and MR staining enriched in CA2. Interestingly, although perineuronal nets (PNNs) are known to surround CA2 cells in mouse and rat, we found that staining for PNNs differed across species in that both CA2 and CA3 showed staining in voles and primarily CA3 in hamsters with only some neurons in proximal CA2 showing staining. These results demonstrate that, like in mouse, CA2 in voles and hamsters can be molecularly distinguished from neighboring CA1 and CA3 areas, but PNN staining is less useful for identifying CA2 in the latter two species. These findings reveal commonalities across species in molecular profile of CA2, which will facilitate future studies of CA2 in these species. Yet to be determined is how differences in PNNs might relate to differences in social behavior across species.
Identification of SARS-CoV-2 Mpro inhibitors through deep reinforcement learning for de novo drug design and computational chemistry approaches
Authors: Hazemann Julien , Kimmerlin Thierry , Lange Roland , Sweeney Aengus Mac , Bourquin Geoffroy , Ritz Daniel , Czodrowski Paul
Published: February 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of coronavirus disease (COVID-19) since its emergence in December 2019. As of January 2024, there has been over 774 million reported cases and 7 million deaths worldwide.[1]While vaccination efforts have been successful in reducing the severity of the disease and decreasing the transmission rate, the development of effective therapeutics against SARS-CoV-2 remains a critical need.[2] The main protease (Mpro) of SARS-CoV-2 is an essential enzyme required for viral replication and has been identified as a promising target for drug development. In this study, we report the identification of novel Mpro inhibitors, using a combination of deep reinforcement learning for de novo drug design with 3D pharmacophore/shape-based alignment and privileged fragment match count scoring components followed by hit expansions and molecular docking approaches. Our experimentally validated results show that 3 novel series exhibit potent inhibitory activity against SARS-CoV-2 Mpro, with IC50 values ranging from 1.3 uM to 2.3 uM and a high degree of selectivity. These findings represent promising starting points for the development of new antiviral therapies against COVID-19.