bluuebunny/crossref_metadata_2025 huggingface dataset:
The neurotoxic effect of Naja nubiae (Serpentes: Elapidae) venom from Sudan
Authors: Khalid Huda , Mukhtar Maowia M
Published: November 2024

Background

Neurotoxicity is a common feature of elapid snake envenomation. There are limited studies on the toxicity of Naja nubiae venom, the Nubian spitting cobra, from north-east Africa.

Methods

We used the chick biventer cervicis nerve-muscle preparation to demonstrate the neurotoxic effect of N. nubiae venom and to compare it with the potent neurotoxic cobra Naja melanoleuca venom. Venoms were separated by successive reverse-phase high-performance liquid chromatography (RP-HPLC) runs and the molecular mass of the neurotoxins was determined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS).

Results

Both venoms caused time-dependent inhibition of nerve-mediated twitches with a t90 value of 22.2±1.9 min and 12.9±1.2 min for N. nubiae and N. melanoleuca venoms, respectively. Prior incubation of some commercial antivenom (EchiTab-Plus-ICP [Costa Rica], CSL, Parkville, Victoria, Australia) and snake venom antisera [India]) did not prevent the neurotoxic effect of N. nubiae venom. The chromatographic separation of N. nubiae and N. melanoleuca venoms followed by MALDI-TOF MS analysis revealed that short-chain α-neurotoxin accounted for 8.4% of N. nubiae and 14.8% of N. melanoleuca whole venoms.

Conclusions

N. nubiae venom, which was previously known as cytotoxic venom, exhibits considerable in vitro neurotoxic effects on chick nerve-muscle preparations that may have consequences for antivenom development in north-east Africa.
Effects of White Noise and Therapeutic Touch on Pain and Comfort in Newborns during Heel Lance
Authors: Erol Duygu Deniz , Özalp Gerçeker Gülçin
Published: November 2024

Background:

Nonpharmacological methods such as white noise and therapeutic touch can be used in pain management in neonates.

Purpose:

This randomized controlled study evaluated the effects of white noise and therapeutic touch during heel lance procedures on pain, comfort levels, and physiological parameters in healthy neonates.

Methods:

This parallel, randomized controlled study was conducted in the Obstetrics and Gynecology Service of a regional hospital. The sample comprised 160 neonates with gestational ages of >35 weeks randomly assigned to 4 groups (white noise [WN], therapeutic touch [TT], white noise + therapeutic touch [WT], and control [CG] group). Pain and comfort levels were evaluated according to the Neonatal Infant Pain Scale, and the COMFORTneo Scale. The primary outcomes were pain and comfort levels, and the secondary outcomes were heart rate and SpO2 levels. The Kruskal-Wallis test was used to compare the scale scores among groups.

Results:

There were significant differences among groups in terms of Neonatal Infant Pain Scale and COMFORTneo scores (P < .05). The pain scores for the white noise, therapeutic touch, and white noise + therapeutic touch groups were 4.2 ± 2.0, 5.2 ± 1.6, and 3.3 ± 1.7, respectively. There was a significant difference in average heart rate during the heel lance procedure among the groups (P < .05). Pain scores of the intervention groups were lower compared to the control group.

Implications for Practice and Research:

The combination of white noise and therapeutic touch was more effective in reducing pain and increasing comfort levels. Nurses could reduce procedural pain by applying these pain relief methods.
Our First Steps
Authors: Kelly Allison Zara , Bagwell Gail A. , Coates-Huffman Penni
Published: November 2024

Background:

In 2020, the rate of newborns diagnosed with neonatal abstinence syndrome (NAS) in the United States was 6.3 for every 1000 newborn hospitalizations. Resources used to care for this population, particularly NICU beds, are being overwhelmed. In 2020, the state of Ohio saw a rate of 9.5 newborns with NAS for every 1000 newborn hospitalizations.

Purpose:

To determine if using the Eat, Sleep, Console (ESC) model of care to guide management of neonates with NAS instead of the Finnegan Scale would reduce the number of admissions of neonates diagnosed with NAS to the neonatal intensive care unit (NICU).

Methods:

The PDSA (Plan, Do, Study, Act) method was used in the planning and implementation of this pilot quality improvement project. Education regarding the ESC model of care was provided to the Mother/Infant Unit (MIU), with ongoing education and resources provided and readily available on the unit.

Results:

Fifteen neonates were managed with ESC. Of the 5 who would have been admitted to the NICU for pharmacological treatment if Finnegan Scores were the determining factor for admission, 2 were discharged home from the MIU having been managed with ESC.

Implications for practice and research:

The use of the ESC model of care can be a useful tool in the management and assessment of neonates with NAS. Resource allocation for care of this population must be assessed to provide optimal non-pharmacological interventions.
Treprostinil Use in the NICU
Authors: Lee Diana
Published: November 2024

Background:

Treprostinil is a prostacyclin analogue that is frequently used in the pediatric and adult population to treat pulmonary hypertension; however, it is not often a drug of choice for patients in the neonatal intensive care unit (NICU).

Purpose:

To evaluate the efficacy of treprostinil as a treatment for pulmonary hypertension of the neonate.

Data Sources:

Electronic databases such as PubMed, CINAHL, and Embase were used for this literature review. Twelve articles within the last 10 years (2014-2024) were included in this review.

Study Selection:

136 articles were identified and primary research studies published in English and with patients younger than one year of age were included. Duplicates were removed and studies discussing genetics and congenital heart disease were excluded.

Data Extraction:

Abstracts were reviewed and articles referencing treprostinil use in the NICU were included for review. Independent extraction was completed by author.

Results:

Findings showed treprostinil to have a therapeutic benefit in infants with congenital diaphragmatic hernias and possibly with premature infants. Some adverse effects were noted, one of which included hypotension; however, management strategies exist to mitigate this effect.

Implications for Practice and Research:

Initiating treprostinil in the NICU may help decrease the severity of persistent pulmonary hypertension of the newborn (PPHN) which can help reduce neonatal morbidity and mortality. Future research is needed to determine the optimal timeframe to initiate treprostinil in the NICU; the duration of treatment; use in other conditions that can cause PPHN (i.e. meconium aspiration syndrome); and the other potential effects it may have for the preterm infant.
Clinical characteristics, prognosis, and prognostic factors of patients with second primary triple-negative breast cancer: a study based on Surveillance, Epidemiology, and End Results database
Authors: Ding Li , Xu Yan , Li Chao , Chen Xi
Published: November 2024

This study examined the characteristics of tumors, treatments, and survival outcomes, with a particular focus on the survival-related factors of second primary triple-negative breast cancer (TNBC) in comparison to first primary TNBC. The Surveillance, Epidemiology, and End Results database was utilized to identify and enroll patients diagnosed with TNBC between the years 2010 and 2015. The outcomes of this study were 3-year and 5-year breast cancer-specific survival (BCSS). The multivariate competing risk model was conducted to explore the association between the second primary cancer and BCSS and to estimate risk factors for BCSS of both first and second primary TNBC. The hazard ratio and 95% confidence interval (CI) were evaluation indices. Our study demonstrated that age, histological grade III/IV, high T stage, high N stage, and TNBC were associated with a decreased 3-year and 5-year BCSS in both first and second primary TNBC. Family income ≥$60 000 per year (hazard ratio: 0.68, 95% CI: 0.48–0.95, P = 0.026) correlated with better 3-year BCSS in patients with second primary TNBC. Breast-conserving surgery, mastectomy, and the interval between two cancer diagnoses >3 years were associated with increased 3-year and 5-year BCSS in patients with second primary TNBC (all P < 0.05). This paper reveals a worse survival of second primary TNBC. Great attention should be paid to the prognosis of patients with second primary TNBC.
An Update on Scholarly Productivity for Physician Assistant/Associate Faculty
Authors: Roberts Amy Lynn , Rizzolo Denise , Bruza-Augatis Mirela , Frias-Sarmiento Dominique
Published: November 2024

Introduction

Prior research has suggested that physician assistant/associate (PA) educators often cannot dedicate sufficient time to research since most of their time is committed to teaching, service, and practicing clinically. Because of the time constraints and lack of scholarship training, PA faculty are not motivated to participate in scholarly activities, resulting in burnout and low productivity.

Methods

This study examined the 2019 PA Education Association Faculty and Directors data set, focusing on descriptive and bivariate analysis of demographic characteristics, highest degree completed, academic rank, years in PA education, primary position within the PA program, and various aspects of scholarship activities such as the number and types of publications.

Results

Nearly half (50.3%) of PA faculty reported publishing during their academic career, with a median of 3 publications in total since the start of their PA education career (interquartile range [IQR], 1–7). The data revealed that the mean number of peer-reviewed articles is 2 (IQR, 1–5), with no books and chapters published. Compared with PAs who did not publish, PA faculty who published were more likely to be male (35.4% vs. 29.1%; P = .035), to hold a doctorate (41.3% vs. 20.3%; P < .001), and to indicate their academic role as a professor (12.4% vs. 4.4%) and associate professor (33.8% vs. 12.3%; P < .001).

Discussion

Although there has been some improvement regarding the number of publications, growth has been significantly slow. Although the reason for this slow growth is multifaceted, gender disparities and time and lack of funding appear to be some of the major reasons.
In Vitro Analysis of Left Ventricular Assist Device Outflow Graft Orientations and Their Effect on Aortic Hemodynamics
Authors: Herz Christopher , Grab Maximilian , Müller Christoph , Hanuna Maja , Kamla Christine-Elena , Clevert Dirk-André , Curta Adrian , Fink Nicola , Mela Petra , Hagl Christian , Grefen Linda
Published: November 2024

Continuous-flow left ventricular assist devices have become an important treatment option for patients with advanced heart failure. However, adverse hemodynamic effects as consequence of an altered blood flow within the aorta and the aortic root remain a topic of concern. In this work, we investigated the influence of the outflow graft orientation on the hemodynamic profile and flow parameters within the thoracic aorta. Aortic models with different outflow graft orientations were designed and three-dimensional (3D) printed to mimic common implantation configurations and were integrated into a pulsatile mock circulatory flow loop. Assist device function was achieved using a rotary pump, replicating nonpulsatile, continuous support flows of 1–5 L/min. Flow velocity, wall shear stress, and pressure gradients were investigated for each configuration using sonography and four-dimensional (4D) flow magnetic resonance imaging. Mean wall shear stresses measured in 4D flow software were lowest for a graft inclination angle of 45°. Streamline visualization revealed areas of nonuniform, retrograde, and vortex flow in all models but most prominent for the aortic model with an outflow graft inclination of 60°. The insights gained from this research may aid in understanding clinical outcomes following assist device implantation and long-term mechanical circulatory support.
The Role of Jail Testing in the Public Health Response to Syphilis in King County, Washington
Authors: Buck Taylor , Herrera Perales Luis Enrique , Berzkalns Anna , Barash Elizabeth , Golden Matthew R. , Dombrowski Julia C.
Published: November 2024

Background

The incidence of syphilis among cisgender women and heterosexual men in the United States has risen sharply. Public Health – Seattle & King County implemented a voluntary, opt-in syphilis screening program in a jail to reach disproportionately affected populations outside the health care system.

Methods

Public Health – Seattle & King County disease intervention specialists conducted syphilis screening 4 days per week in a regional jail. All persons screened January 2022 to March 2023 were included in the analysis. Disease intervention specialists performed point-of-care treponemal-specific tests, collected demographic and risk factor data, worked with jail medical providers to coordinate empiric treatment and confirmatory testing, and determined syphilis history and stage. We categorized persons with reactive rapid tests as “confirmed,” “presumed,” “possible,” or “not new” cases based on confirmatory testing and syphilis history. We compared the characteristics of confirmed cases to overall King County syphilis cases using χ
2 tests and examined treatment completion by diagnosis category.

Results

A total of 1371 persons completed screening; 69 (5.0%) had positive results, of whom 51 (73.9%) had confirmatory testing, and 33 had confirmed infections (2.4% of screened persons). Compared with all King County syphilis cases, confirmed cases were more likely to be cisgender women (30.3% vs. 21.9%) or cisgender heterosexual men (66.7% vs. 20.6%), people living homeless (66.7% vs. 24.3%), or people who use methamphetamine (90.9% vs. 20.3%; P < 0.001 for all comparisons). Among 33 persons with confirmed syphilis, 29 (87.8%) started and 18 (54.5%) completed treatment.

Conclusions

Jail screening reached persons at disproportionate risk for syphilis, but treatment was often incomplete.
Where next for contact lens research?
Authors: Papas Eric B.
Published: November 2024

VIRTUAL ISSUE EDITORIAL

This editorial fronts the second virtual issue for Optometry & Vision Science. Virtual issues are a collection of papers from previously published issues of the journal that are brought together in a single, online publication. They highlight the important contribution the journal has made in supporting contact lens research. All the papers referenced and previously published in Optometry & Vision Science will be made free access for 1-month. The collection can be accessed here: https://journals.lww.com/optvissci/pages/collectiondetails.aspx?TopicalCollectionId=18
Incidence and treatment of complex regional pain syndrome after surgery: analysis of claims data from Germany
Authors: Teichmüller Karolin , Rose Norman , Dreiling Johannes , Schwarzkopf Daniel , Meißner Winfried , Rittner Heike L. , Kindl Gudrun
Published: November 2024

Introduction:

Complex regional pain syndrome (CRPS) is a rare complication after limb injuries. Early recognition of the symptomatology and interdisciplinary interventions are essential to prevent long-term disability and pain.

Objective:

This article presents results on the incidence of CRPS after surgery in Germany and treatments used by patients with CRPS, using claims data from the BARMER, a German nationwide health care insurance.

Methods:

A total of N = 85,862 BARMER patients with inpatient surgery on the upper or lower limb in 2018 were included. Patients with CRPS were identified by documented International Statistical Classification of Diseases and Related Health Problems
-10 diagnosis within 12 months after surgery. For the same period, medication and nonpharmaceutical therapies for inpatient and outpatient care were assessed.

Results:

The overall incidence of CRPS within 12 months after surgery was 0.34%. With 0.60%, the incidence of CRPS after surgeries of the upper limb was 3 times higher than after lower-limb surgeries (0.20%). Women were more frequently affected, and most patients were between 50 and 70 years old. About 80% to 90% of patients with CRPS received physiotherapy and nonopioid pain medication within 12 months after surgery. Approximately 40% to 50% were treated with opioids and/or antineuropathic medication. Cortisone, bisphosphonates, pain therapy, and occupational therapy were rarely claimed.

Conclusion:

We found a low incidence of CRPS after various types of surgeries. Although previous research has focused on distal radius fractures and ankle surgery, our data suggest that clinicians should be aware of CRPS after other types of surgeries as well. Real-world treatment of CRPS does not reflect recommendations in clinical practice guidelines.
“The Septum and Nasomaxillary Vault Associated with Unrepaired Unilateral Cleft Lip and Palate: A Data-Driven 3D Model”
Authors: Linkugel Andrew D. , Mercan Ezgi , Tolley Philip D. , Roy Mélissa , Ettinger Russell E. , Lo Lun-Jou , Kane Alex A. , Tse Raymond W.
Published: November 2024

Background:

Defining the nature of the unilateral cleft lip and palate nasal deformity (uCLND) and its optimal surgical correction continues to be a challenge. The purpose of this study was to develop a data-driven model of the primary unrepaired osseocartilaginous skeleton of the nasomaxillary complex.

Methods:

CT scans of nineteen 3-month-old infants with unrepaired unilateral cleft lip and palate and nineteen age- and race-matched controls were analyzed. Osseous landmark deviation in subjects with clefts was compared to controls. Segmentation of the osseocartilaginous septum was performed, and deformational differences were calculated between cleft and non-cleft cohorts.

Results:

Compared to controls, the rhinion, non-cleft nasomaxillary junction, and cleft nasomaxillary junction deviated towards the non-cleft side. The piriform margins each diverge away from midline with the non-cleft side deviating lateral and superior, and the cleft side deviating lateral and posterior. These alterations result in a bony torsion with sigmoidal configuration of the cleft side aperture, vertical shortening of the central midface, and de-projection of the nasal pyramid. Segmentation of the septum revealed anterior deviation toward the non-cleft side with a single convexity toward the cleft.

Conclusions:

This three-dimensional data-driven model contradicts prior models and confirms a collapsing twist of the cleft side aperture and medialization of the bony margin of the nasal airway with deviation of the nasal bone complex toward the non-cleft side. This analysis defines the critical anatomic characteristics of the cleft nasal deformity and informs the goals of nasal correction at the time of primary repair.
Lipophagy Enhances Fat Graft Retention by Stimulating Dedifferentiation of Mature Adipocytes and Modulating Inflammation
Authors: Xu Shujie , Wang Xinhui , Xu Yidan , Yang Han , Liao Yunjun , Chang Qiang , Cai Junrong , Lu Feng , Gao Jianhua , Yuan Yi
Published: November 2024

Background:

Maintaining lipid metabolic homeostasis is essential for cells to respond to environmental stresses, ensure survival, and preserve functionality. Lipophagy, a form of autophagy in which intracellular lysosomes target and degrade lipid droplets. The authors hypothesize that pharmacologically enhancing or disrupting lipophagy could either improve or impair the retention rates of fat grafts.

Methods:

Human fat graft nodules, retained for six months, were collected through surgical procedures for analysis. Additionally, a mouse fat graft model was established by mixing fragmented adipose tissue with the autophagy inducer rapamycin (Rapa), the autophagy inhibitor 3-methyladenine (3-MA), or PBS, and subcutaneously implanting into the bilateral lower back of mice for localized activation or inhibition of lipophagy. Samples were collected at various time points for morphological, histological, transcriptomic, and gene expression analysis.

Results:

A significant increase in lipophagy was demonstrated in both human and mouse fat grafts. Rapa-induced upregulation of lipophagy promoted long-term retention of mouse fat grafts and resulted in fewer cysts and reduced fibrosis. Lipophagy activation facilitated the dedifferentiation of mature adipocytes and adipogenesis. Moreover, lipophagy enhanced the metabolism of oil droplets in macrophages. Activation of lipophagy also reduced long-term macrophage infiltration and collagen deposition in fat grafts while simultaneously increasing the proportion of M2 macrophages.

Conclusion:

Lipophagy was activated following fat grafting. Lipophagy improves fat graft retention and quality by stimulating the dedifferentiation of mature adipocytes, promoting oil metabolism, and reducing inflammation. Thus, lipophagy serves as a crucial integrative point connecting lipid metabolism, regeneration, and immunity in fat grafts.
Risk of Contrast-Induced Acute Kidney Injury in Computed Tomography
Authors: Choi Byungjin , Heo Subin , Mcdonald Jennifer S. , Choi Sang Hyun , Choi Won-Mook , Lee Jung Bok , Lee Eunyoung Angela , Park Seong Ho , Seol Soobeen , Gan Sujin , Park Bumhee , Choi Hee Jung , Kim Byoung Je , Rhee Sang Youl , Hong Seung Baek , Kim Kyung-Hee , Lee Young Hwan , Kim Seung Soo , Park Rae Woong
Published: November 2024

Objectives

Concern about contrast-induced acute kidney injury (CI-AKI) may delay the timely administration of contrast media for computed tomography (CT). The precise causative effect of iodinated contrast media on CI-AKI and its relevant risk factors remains an area of ongoing investigation. Therefore, this study aimed to determine the risk of CI-AKI following contrast-enhanced CT and its predisposing risk factors.

Materials and Methods

This study employed a 1:1 propensity score matching analysis using electronic medical records gathered between January 2006 and December 2022 from 16 institutions in South Korea. Contrast-enhanced and nonenhanced CT scans in patients aged 18 years and above were matched for baseline estimated glomerular filtration rate (eGFR), demographic characteristics, and clinical variables to assess the risk of CI-AKI. Subgroup analyses were conducted to evaluate any significant risk factors for CI-AKI.

Results

A total of 182,170 CT scans with contrast were matched to 182,170 CT scans without contrast. The risk of CI-AKI in the entire study cohort was not statistically significant (odds ratio [OR], 1.036; 95% confidence interval [CI], 0.968–1.109; P = 0.34). Subgroup analyses revealed a significantly higher risk of CI-AKI in patients with eGFR <30 mL/min/1.73m2 (OR, 1.176; 95% CI, 1.080–1.281; P = 0.011) or eGFR 30–45 mL/min/1.73m2 (OR, 1.139; 95% CI, 1.043–1.244; P = 0.019), patients diagnosed with chronic kidney disease (OR, 1.215; 95% CI, 1.084–1.361; P = 0.011), and those administered with iso-osmolar contrast media (OR, 1.392; 95% CI, 1.196–1.622; P = 0.011).

Conclusions

The risk of CI-AKI following CT was minimal in the general population. However, caution is warranted for patients with chronic kidney disease and eGFR lower than 45 mL/min/1.73m2, or those administered with iso-osmolar contrast media.
Ovarian Clear Cell Adenocarcinoma With Low 68Ga-FAPI-46 and Low 18F-FDG Uptake on PET/CT
Authors: Bentestuen Morten , Sylvest Camilla , Frandsen Anna Poulsgaard , Zacho Helle D.
Published: November 2024

A 67-year-old woman presented with a 12 × 20 × 24-cm adnexal tumor. Ultrasonography revealed an irregular, multilocular tumor, with increased flow in the solid components, and ascites—features that are consistent with ovarian cancer. The patient underwent 18F-FDG PET/CT and 68Ga-FAPI-46 PET/CT, both of which showed low uptake values. Histopathology confirmed ovarian clear cell adenocarcinoma (OCCC), a less common subtype that is underrepresented in FAPI PET/CT studies so far. Low 18F-FDG uptake is a known feature of OCCC and has been previously reported; however, this case identifies OCCC as a potential pitfall in 68Ga-FAPI-46 PET/CT.
Effect of Transpancreatic Mattress Suture With Polyglycolic Acid Sheet in Pancreatic Stump Closure for the Prevention of Postoperative Pancreatic Fistula in Robotic Distal Pancreatectomy
Authors: Murata Yasuhiro , Komatsubara Haruna , Noguchi Daisuke , Ito Takahiro , Hayasaki Aoi , Iizawa Yusuke , Fujii Takehiro , Tanemura Akihiro , Kuriyama Naohisa , Kishiwada Masashi , Mizuno Shugo
Published: November 2024

Objective:

Pancreatic stump closure in minimally invasive distal pancreatectomy (DP) commonly utilizes staplers due to its simplicity; however, postoperative pancreatic fistula (POPF) remains the most frequent complication. We have developed a novel stump closure technique using a transpancreatic mattress suture with a polyglycolic acid sheet (TP method) under robotic DP. This study aims to evaluate the efficacy of the TP method.

Materials and Methods:

This study included 145 cases of pure minimally invasive DP performed between February 2011 and July 2024: 34 robotic (R) and 97 laparoscopic (Lap). Surgical outcomes were compared across 3 groups based on the stump closure method: 18 cases using the TP method (TP group; R: 18), 22 with hand-sewn closure in a fish-mouth manner (FM group; Lap: 22), and 91 with a reinforced stapler (S group; R: 16, Lap: 75). Logistic regression analysis was employed to identify risk factors for POPF.

Results:

POPF occurred in 20 of 131 cases (grade B: 19, C: 1, 15.3%). The TP group exhibited the lowest POPF rate (TP vs FM vs S: 5.6% vs 27.3% vs 14.3%). Multivariate analysis identified pancreatic thickness ≥12 mm as an independent risk factor. For thickness <12 mm, no significant differences in POPF rates were observed (TP vs FM vs S: 0% vs 25.0% vs 5.6%). However, for thickness ≥12 mm, the TP group had a significantly lower POPF rate compared with the S group (TP vs FM vs S: 7.7% vs 28.6% vs 47.4%).

Conclusion:

The TP method is superior to stapler closure in preventing POPF, especially in cases with pancreatic thickness of ≥12 mm.
Does greater variation reside in the larger sex?
Authors: Halsey Lewis G. , Giofrè David , Geary David C.
Published: November 2024

The question of whether males or females are the more variable sex is long-standing, and yet to be fully answered. We investigate the relationships between body mass and variation across species using a phylogenetically informed analysis of the body mass of 337 species representing six mammalian orders. Within each order, we found that the larger sex is typically the more variable sex, whether male or female, and the variation–size relationship is arguably often close to unity. Thus, size may be the main or even sole driver of variability in at least some orders. Deviations from the expected 1 : 1 relationship emerged, however, in regressions of male : female mass variance against male : female mean mass, for Chiroptera and Rodentia, which both presented hyperallometric relationships suggesting that drivers over and above size influence differences in variation between the sexes. In Chiroptera, most species have larger females. The
y
-intercept value for Artiodactyla and Primates were significantly greater than 0 suggesting greater male variation in species where the sexes are of commensurable size. Historic belief of exclusively greater male variability may have resulted from a focus on species with intense male–male competition and, thus, larger male body sizes. Our results suggest that it is often size, not sex
per se
, that influences within-sex variability, although additional sex-specific factors might be present in at least some orders.
Within-host dynamics of antiviral treatment with remdesivir for SARS-CoV-2 infection
Authors: Schuh Lea , Markov Peter V. , Voulgaridi Ioanna , Bogogiannidou Zacharoula , Mouchtouri Varvara A. , Hadjichristodoulou Christos , Stilianakis Nikolaos I.
Published: November 2024

The effectiveness of antiviral treatment with remdesivir against COVID-19 has been investigated in clinical trials suggesting earlier recovery. However, this effect seems to be rather modest. In this study, we tracked the clinical course of SARS-CoV-2 infections in 369 COVID-19 individuals across a spectrum of illness severities, including both untreated individuals and individuals who received antiviral treatment with remdesivir. Moreover, using a process-based mathematical model, we quantified and analysed the within-host infection dynamics of a total of 88 individuals, of which 69 were untreated and 19 antiviral-treated individuals. For untreated individuals, we found that those hospitalized exhibit lower levels of early immune response and higher cumulative viral loads than those who were not. For treated individuals, we found that those who died were on average hospitalized later after symptom onset than those who survived, underscoring the importance of early medical intervention for severe COVID-19. Finally, our model estimates a rather limited antiviral activity of remdesivir. Our results provide valuable insights into the clinical course of COVID-19 during antiviral treatment with remdesivir and suggest the need for alternative treatment regimens.
Aurodox inhibits type III secretion in multiple Gram-negative pathogens
Authors: Mark David R. , O’Boyle Nicky , Wale Kabo R. , Tucker Samantha K. , McHugh Rebecca E. , Roe Andrew J.
Published: November 2024

Gram-negative pathogens pose a significant threat due to their propensity for causing various infections, often coupled with formidable resistance to conventional antibiotic treatments. The development of antivirulence (AV) compounds emerges as a promising alternative strategy by disrupting virulence mechanisms rather than targeting bacterial viability. Aurodox has exhibited promising AV properties in previous studies by blocking the expression and function of the LEE-encoded type 3 secretion system (T3SS) in enterohaemorrhagic
Escherichia coli
, an injectosome that translocates effector proteins directly into host target cells. However, aurodox’s efficacy against the T3SS of other pathogens remained unanswered. Using quantitative real-time polymerase chain reaction, we show that aurodox exerts inhibitory effects on selected T3SS including those of
Salmonella
Typhimurium,
Yersinia pseudotuberculosis
and
Vibrio parahaemolyticus
. Imaging of RAW 264.7 cells infected with
S
. Typhimurium showed that aurodox protects against late stages of infection by blocking the expression of the SPI-2 T3SS. To elucidate a conserved mechanism of action, we compared transcriptomic datasets from both
E. coli
and
S
. Typhimurium treated with aurodox to identify orthologous genes differentially expressed in response to aurodox treatment across both pathogens. This study sheds light on potential mechanisms driving the action of this promising AV compound.
Turing patterns on discrete topologies: from networks to higher-order structures
Authors: Muolo Riccardo , Giambagli Lorenzo , Nakao Hiroya , Fanelli Duccio , Carletti Timoteo
Published: November 2024

Nature is a blossoming of regular structures, signature of self-organization of the underlying microscopic interacting agents. Turing theory of pattern formation is one of the most studied mechanisms to address such phenomena and has been applied to a widespread gallery of disciplines. Turing himself used a spatial discretization of the hosting support to eventually deal with a set of ODEs. Such an idea contained the seeds of the theory on discrete support, which has been fully acknowledged with the birth of network science in the early 2000s. This approach allows us to tackle several settings not displaying a trivial continuous embedding, such as multiplex, temporal networks and, recently, higher-order structures. This line of research has been mostly confined within the network science community, despite its inherent potential to transcend the conventional boundaries of the PDE-based approach to Turing patterns. Moreover, network topology allows for novel dynamics to be generated via a universal formalism that can be readily extended to account for higher-order structures. The interplay between continuous and discrete settings can pave the way for further developments in the field.
Oscillations and tipping points in a model thermokinetic reaction
Authors: Salzman Shontae , Forbes Lawrence K. , Quinn Courtney
Published: November 2024

We consider a model thermokinetic reaction that is both autocatalytic and temperature sensitive. The mechanism consists of two reactions. The first is a reversible reaction with a temperature-dependent rate, and the second involves a cubically autocatalytic process. We demonstrate the presence of up to five steady states in the system, dependent on parameters, and we illustrate the fact that the system can exhibit tipping-point behaviour, in which small changes to initial conditions in an experiment could lead to radically different long-term outcomes. We prove that oscillatory behaviour is not possible over large regions in the parameter space; outside these regions, however, oscillations have been found, and we present a simple and robust method for computing them. Small-amplitude oscillations can arise through Hopf bifurcations at an equilibrium point. In addition, large-amplitude oscillations can bifurcate directly from global structures that are associated with equilibria behaving as saddles. This is illustrated with some numerical solutions of these highly nonlinear equations.
Biomechanical drivers of the evolution of butterflies and moths with a coilable proboscis
Authors: Palaoro Alexandre V. , Monaenkova Daria , Beard Charles E. , Adler Peter H. , Kornev Konstantin G.
Published: November 2024

Current biomechanical models suggest that butterflies and moths use their proboscis as a drinking straw pulling nectar as a continuous liquid column. Our analyses revealed an alternative mode for fluid uptake: drinking bubble trains that help defeat drag. We combined X-ray phase-contrast imaging, optical video microscopy, micro-computed tomography, phylogenetic models of evolution and fluid mechanics models of bubble-train formation to understand the biomechanics of butterfly and moth feeding. Our models suggest that the bubble-train mechanism appeared in the early evolution of butterflies and moths with a proboscis long enough to coil. We propose that, in addition to the ability to drink a continuous column of fluid from pools, the ability to exploit fluid films by capitalizing on bubble trains would have expanded the range of available food sources, facilitating diversification of Lepidoptera.
Day-to-day associations between testosterone, sexual desire and courtship efforts in young men
Authors: Catena Tikal , Crewther Blair T. , Eisenbruch Adar B. , Grillot Rachel L. , Maestripieri Dario , Roney James R.
Published: November 2024

Testosterone plays important roles in reproductive behaviour in many species. Despite a common belief that testosterone regulates fluctuations in human sexual desire, there is little direct evidence that relates within-person changes in natural testosterone production to within-person changes in sexual desire. Here, we measured daily salivary testosterone concentrations from 41 adult men for one month, along with daily self-reports of sexual desire (
n
= 759 observations for the main analyses). We analysed concurrent relationships between within-person changes in testosterone and desire, and also lagged relationships that were analysed using a continuous-time modelling framework. We found no evidence for significant, positive relationships between testosterone and desire, which argues against the notion that day-to-day changes in eugonadal men’s baseline testosterone regulates changes in their sexual desire. However, additional analyses provided preliminary evidence for a positive relationship between testosterone and self-reported courtship effort, particularly on days when single participants interacted with potential romantic partners. Our findings add original evidence regarding day-to-day associations between testosterone and desire, and suggest that testosterone above minimum threshold concentrations does not increase sexual desire. We propose that the evolved functions of testosterone in human males are more closely associated with courtship efforts than with sexual desire.
Predicting Unintended Pregnancy in Senegal by using Machine Learning Models: Evidence from Senegal DHS 2023
Authors: Khan Majlish Mushfiqur Rahman , Tawhid Sultanul Arafean , Kibria Gulam , Sakib Nazmus
Published: November 2024

Unintended pregnancy refers to a pregnancy that is either mistimed or unwanted at the time of conception. Such pregnancies can have harmful effects, including negative impacts on maternal and child health, economic hardship, and strained relationships. This study aims to assess the effectiveness of machine learning algorithms in forecasting unintended pregnancies in Senegal and identifying the key factors that significantly impact them. The study utilized data from the 2023 Senegal Demographic and Health Survey, focusing on pregnant women. A final sample of 885 respondents was analyzed after handling missing values and six machine learning models namely Logistic Regression, Random Forest, K-Nearest Neighbors, Support Vector Machine, Naïve Bayes and Extra Tree Classifier was used. The Random Forest algorithm emerged as the best predictive model due to its highest AUC value (80.45%), surpassing all other machine learning algorithms used in this study. Total birth, currently residing with husband/partner, respondent’s education level, number of living children, Husband/partner’s occupation, residence type, Respondent can refuse sex and intention of contraceptive use are identified as contributing factors in that predict unintended pregnancy. The study’s results suggest that machine learning models, particularly Random Forest, can significantly enhance predictive accuracy for unintended pregnancies, helping public health initiatives in Senegal target at-risk populations. By identifying women at risk of unplanned pregnancies, targeted interventions and support services can be implemented, ultimately improving maternal health outcomes.
The N-terminal Domain of cpTatC Protein Interacts with the Precursor Mature Domain in Chloroplast TAT Translocation
Authors: Maddethalawe Thilini , Hird Krystina , Dabney-Smith Carole
Published: November 2024

The chloroplast Twin Arginine Transport (cpTAT) protein translocation pathway is one of the thylakoid membrane’s two protein transport pathways for getting proteins into the lumen. The cpTAT system distinguishes itself by transporting fully folded proteins across the thylakoid, using the sole energy source of the proton motive force (PMF). The cpTAT pathway is evolutionarily conserved with the TAT pathway found in many bacteria and archaea. Although small differences exist, TAT systems in different organisms share homologous protein composition and similar molecular mechanisms. The cpTAT system comprises cpTatC, Hcf106, and Tha4 (the prokaryotic homologs of these proteins are TatC, TatB, and TatA, respectively). (cp)TatC is one of the essential proteins in the (cp)TAT system, as it is present in the receptor complex. The amino acid sequence alignment of cpTatC and TatC protein in archaea andE. colihas shown a unique N-terminal amino acid extension of 70-100 amino acids in mature cpTatC that is not present in prokaryotic TatC. However, the role of the amino-terminal extension in cpTatC function is still unknown. We present crosslinking evidence that the amino-terminal extension directly interacts with the precursor mature domain during TAT protein translocation and may serve to prime the transporter with bound precursor in the absence of the PMF.

Highlights

The cpTatC protein in the cpTAT pathway has a unique amino-terminal extension not found in bacterial or archaeal TatC proteins.

The N-terminal extension of cpTatC interacts with the precursor mature domain during TAT translocation.

The crosslinking data indicate that different regions within the N-terminal extension exhibit varying intensities when binding to the precursor.
Hepatitis B core-related antigen (HBcrAg) point-of-care tests as a risk stratification tool: experience from Kenya
Authors: Downs Louise O , Okanda Dorcas , Chirro Oscar , Zaharani Mwanakombo , Safari Benson , Aliyan Nadia , Andersson Monique I , Tanaka Yasuhito , Etyang Anthony O , Shimakawa Yusuke , Githinji George , Matthews Philippa C
Published: November 2024

We undertook a point-of-care test (POCT) for hepatitis B core-related antigen (HBcrAg) on adults living with HBV in Kilifi, Kenya. A positive test identified all with hepatitis B viral load >200,000 IU/ml, who were HBeAg positive, and correlated with higher ALT (p = 0.03), raised APRI (p<0.001) and elastography scores (p = 0.03).
Deep Learning-based Real-Time Seizure Detection and Multi-Seizure Classification on Pediatric EEG
Authors: Jeong Hyewon , Lee Kwanhyung , Kim Seyun , Kang Hoon-Chul , Yang Donghwa
Published: November 2024

Background and Objective

To develop a reliable and accurate seizure detection method using deep learning models capable of detecting and classifying multiple seizure types in real time.

Methods

We retrospectively collected electroencephalography (EEG) recordings, which were acquired as part of routine diagnostic tests for patients aged 3 months to ≤18 years of age with childhood absence epilepsy, infantile epileptic spasms syndrome, other generalized epilepsy, and focal epilepsy, between January 2018 and December 2022 at Severance Children’s Hospital. We used EEG recordings from both seizure and non-seizure patients, which were downsampled to 200 Hz for real-time seizure detection and multi-classification.

Results

Of the 199 patients (620 seizures), 49 (297 seizures) belonged to the childhood absence epilepsy group, 16 (200 seizures) to the infantile epileptic spasms syndrome group, 14 (76 seizures) to other generalized epilepsy group, 19 (47 seizures) to focal epilepsy group, and 101 to the normal group. The results showed the best overall performance of AUROC 0.98 and APROC of 0.73 with ResNet with Long-Short Term Network and a 12 s sliding window on real-time seizure detection task. Furthermore, ResNet50 without the frequency bands feature extractor showed the best overall weighted performance for multi-class seizure detection with 0.99 AUROC and 0.99 APPRC.

Discussion

Our approach proposes robust methods which include EEG preprocessing strategy with real-time detection/classification of multiple seizures, which helps monitor pediatric seizure. The result shows that real-time seizure detection can be effectively applied to real-world clinical datasets from a pediatric epilepsy unit with realistic performance and speed.
Assessment of population exposure to pesticide applications with a high-resolution map of pesticide use intensity for mainland France
Authors: Nowak Benjamin , Marliac Gaëlle
Published: November 2024

While there is a lively debate about the potential harmful effects of pesticide use, the multiplication of data sources offers new ways of assessing these effects. To facilitate future studies, this article sets out a method for obtaining a map of pesticide use intensity for mainland France, taking into account the effect of each plot. To do so, a number of pesticide treatments was assigned to each plot based on statistical data concerning the average number of treatments per crop and per region. The final result is a raster with a resolution of 100m, which takes into account the average of treatments for the years 2019, 2020 and 2021. A first application conducted in this study showed that 25% of the French population was exposed to at least 1 pesticide treatment per year in their place of residence (5% exposed to at least 10 treatments per year). There were marked differences in exposure between regions, with particularly high exposure in the west and north of France, for example. The map of pesticide use intensity in France produced in this study is freely accessible for future studies.
Targeting the menopause transition with metformin improves breast cancer outcomes, but discontinuation has deleterious effects on metabolic health: Findings from a preclinical model of postmenopausal breast cancer
Authors: Corleto Karen A. , Schedin Pepper , Kotta Anuhya S. , Strandmo Jenna L. , Foster Samantha M. , Lammoglia Nanci , Karmakar Moumita , Carroll Raymond J. , MacLean Paul S. , Giles Erin D.
Published: November 2024

Background

Women with obesity and/or type-II-diabetes have an increased breast cancer risk, increased metastasis, and poorer prognosis, especially after menopause. In a rat model of high-fat-diet and menopause-induced weight gain, we previously reported that treatment with the anti-diabetic drug metformin for 8-weeks after ovariectomy (OVX; modeling menopause) reduced growth of existing mammary tumors and inhibited new tumor formation. This identified the menopause transition as a potential window-of-opportunity for interventions to decrease obesity-associated breast cancer incidence and disease progression. Here, we extend these findings to determine if limiting metformin to the peak window of OVX-induced weight gain would have similar anti-cancer effects.

Findings

Metformin during the first four weeks following OVX is critical to reducing tumor burden, as rats treated with metformin early (weeks0-4-postOVX) had reduced tumor burden. Conversely, initiating metformin later in the postOVX period (weeks 4-8postOVX) did not reduce cancer burden. Despite improved tumor outcomes, metformin withdrawal after the early postOVX time had detrimental metabolic effects, including weight gain and increased adiposity, insulin, IGF1, and HOMA-IR, which correlate with increased cancer risk.

Conclusions

These data reveal early-postmenopause as a critical window when metformin decreases progression of existing disease and highlights the importance of maintaining treatment to prevent metabolic dysregulation, which could promote secondary tumors/metastasis. These findings also help explain the disconnect between epidemiological studies reporting anticancer benefits of metformin and more recent clinical trials that failed to see similar efficacy, potentially due to issues of timing and/or inclusion of women outside the early postmenopausal window and/or without underlying metabolic dysfunction.
Leveraging Experimental Vasculature Data for High Resolution Brain Tumor Simulations
Authors: Behle Eric , Herold Julian , Schug Alexander
Published: November 2024

Cancer remains a leading cause of mortality. Multidisciplinary studies probe its complex pathology to increase treatment options. Computational modeling of tumor growth on high-performance computing resources offers microscopic insight into its progress and a valuable avenue for advancing our understanding. However, the effective initialization and parameterization of the underlying models require high-resolution data from real tissue structures. Here, we leveraged high performance computing resources and a massive dataset of a mouse brain’s entire vascular network. We processed these image stacks into detailed three-dimensional representations, identified brain regions of interest, and conducted a series of large-scale simulations to investigate how tumor growth is influenced by local vascular network characteristics. By simulating tumor growth with sub-cellular resolution, we can probe to which extent vessel density and vessel network length influence tumor growth. We determined that vessel density is the primary determinant of growth rate. Finally, our results allowed us to extrapolate tumor cell growth predictions for the entire mouse brain, highlighting the critical role of vascular topology in tumor progression. Such increasingly realistic simulations of cancer cells and their microenvironment enable researchers to increasingly bridge the gap between basic biology and clinical practice, ultimately supporting the development of more effective personalized cancer therapies.