bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of peritoneal dialysis strategy on technique and patient survival
Authors: Sanchez Jose Emilio , Ulloa Catalina , Bueno Carmen Merino , Astudillo Elena , Rodríguez-Suárez Carmen
Published: July 2023

Background

The aim of this study was to evaluate the impact of peritoneal dialysis (PD) strategy on technique and patient survival.

Methods

This was a retrospective, single-center study conducted on consecutive patients with chronic kidney disease who underwent PD between January 2009 and December 2019. The study sample was stratified into four different groups according to PD technique [automated (APD) or manual (CAPD)] and icodextrin use (yes versus no). The primary endpoints were survival of both technique and patient.

Results

A total of 531 patients were included in the analysis. Mean ± standard deviation age was 60.6 ± 14.6 years, 68.4% (363) were men and 34.8% (185) had diabetes. The median technique survival time was 19 (15) months. A total of 185 (34.8%), 96 (18.1%), 99 (18.7%) and 151 (28.4%) patients were included in the CAPD/No-Icodextrin, CAPD/Icodextrin, APD/No-Icodextrin and APD/Icodextrin study groups, respectively. Throughout the study, 180 (33.9%) patients underwent renal transplant, 71 (13.4%) were changed to hemodialysis and 151 (28.4%) died. Age [hazard ratio (HR) 0.975, 95% confidence interval (CI) 0.960–0.990, P = .001] and incidence of early peritoneal infection (HR 2.440, 95% CI 1.453–4.098, P = .001) were associated with technique survival, while age (HR 1.029, 95% CI 1.013–1.045, P < .001), Charlson Index (HR 1.192, 95% CI 1.097–1.295, P < 0.001), use of icodextrin (HR 0.421, 95% CI 0.247–0.710, P < .001) and APD/Icodextrin (HR 0.499, 95% CI 0.322–0.803, P = .005) were associated with patient survival.

Conclusions

Icodextrin use and APD/Icodextrin had a positive impact on patient survival, while older age and higher Charlson Index had a negative one. Age and incidence of early peritoneal infection significantly impacted on technique survival.
Elastin‐like polypeptide delivery of anti‐inflammatory peptides to the brain following ischemic stroke
Authors: Howell John Aaron , Gaouette Nicholas , Lopez Mariper , Burke Stephen P. , Perkins Eddie , Bidwell Gene L.
Published: July 2023

Inflammatory processes are activated following ischemic stroke that lead to increased tissue damage for weeks following the ischemic insult, but there are no approved therapies that target this inflammation‐induced secondary injury. Here, we report that SynB1‐ELP‐p50i, a novel protein inhibitor of the nuclear factor kappa B (NF‐κB) inflammatory cascade bound to the drug carrier elastin‐like polypeptide (ELP), decreases NF‐κB induced inflammatory cytokine production in cultured macrophages, crosses the plasma membrane and accumulates in the cytoplasm of both neurons and microglia in vitro, and accumulates at the infarct site where the blood–brain barrier (BBB) is compromised following middle cerebral artery occlusion (MCAO) in rats. Additionally, SynB1‐ELP‐p50i treatment reduces infarct volume by 11.86% compared to saline‐treated controls 24 h following MCAO. Longitudinally, SynB1‐ELP‐p50i treatment improves survival for 14 days following stroke with no effects of toxicity or peripheral organ dysfunction. These results show high potential for ELP‐delivered biologics for therapy of ischemic stroke and other central nervous system disorders and further support targeting inflammation in ischemic stroke.
Controversies and strengths of robot-assisted mastectomy
Authors: Kim Joo Heung , Toesca Antonio , Pozzi Giada , Gazzetta Guglielmo , Marrazzo Emilia , Park Hyung Seok
Published: July 2023

Nipple-sparing mastectomy (NSM) is used to improve cosmetic outcomes while maintaining oncological safety in patients with early breast cancer; however, NSM requires a higher level of skill and workload than mastectomy and is associated with long, visible scars. Robotic surgical systems reduce surgeon workload and facilitate precise surgery. Considering the increasing support of robot-assisted NSM (RNSM), this paper aims to discuss the current controversies based on the research findings reported thus far.

There are four concerns regarding RNSM; increased cost, oncological outcomes, the level of experience and skill, and standardization. It should be noted that RNSM is not a surgery performed on all patients but rather a procedure performed on selected patients who meet specific indications. A large-scale randomized clinical trial comparing robotic and conventional NSM has recently begun in Korea; therefore, it is necessary to wait for these results for more insight into oncological outcomes. Although the level of experience and skill required for robotic mastectomy may not be easily achieved by all surgeons, the learning curve for RNSM appears manageable and can be overcome with appropriate training and practice. Training programs and standardization efforts will help improve the overall quality of RNSM.

There are some advantages to RNSM. The robotic system provides improved precision and accuracy, helping remove breast tissue more effectively. RNSM has advantages such as smaller scars, less blood loss, and a lower rate of surgical complications. Patients who undergo RNSM report better quality of life.
Molecular characteristics and prognosis of breast cancer patients with different level of HER2 positivity after adjuvant and neoadjuvant chemotherapy
Authors: Tuluhong Dilihumaer , Li Xinfang , Gao Hongyu , Zhu Yueyun , Li Qiurong , Wang Shaohua
Published: July 2023

Purpose

HER2-low breast cancer (BC) has renewed interests of researchers worldwide. Here, we aimed to investigate the clinicopathological characteristics of patients with HER2-low, HER2-0 and HER2 ultra-low BC and make conclusion.

Methods

We collected cases of patients who were diagnosed as BC at Jingling General hospital. Immunohistochemistry was used to redefine HER2 scores. Kaplan–Meier methods and Cox proportional hazards regression analysis were used to compare survival.

Results

We found that HER2-low BC was more frequent in hormone receptor (HR)–positive BC patients and was associated with fewer T3-T4, lower breast conserving surgery rate and higher adjuvant chemotherapy rate. HER2-low BC patients had better overall survival (OS) compared to HER2-0 BC in premenopausal and stage II BC. Furthermore, HER2-0 BC patients had lower Ki-67 expression levels compared to HER2-ultra low and HER2-low BC in HR–negative BC. HER2-0 BC patients also had worse OS rate compared to those with HER2-ultra low BC in HR–positive BC. Finally, HER2-0 BC patients showed a higher pathological response rate compared to those with HER2-low BC after neoadjuvant chemotherapy.

Conclusions

These findings suggest that HER2-low BC has distinct biology and clinical features compared to HER2-0 BC, and more investigation is needed to understand the biology of HER2-ultra low BC.
Additive effect of histamine and muscimol upon induction of antinociceptive and antidepressant effects in mice
Authors: Baghani Matin , Fathalizade Farzan , Khakpai Fatemeh , Fazli-Tabaei Soheila , Zarrindast Mohammad-Reza
Published: July 2023

We investigated the effects of histamine and GABAA receptor agents on pain and depression-like behaviors and their interaction using a tail-flick test and the forced swimming test (FST) in male mice. Our data revealed that intraperitoneal administration of muscimol (0.12 and 0.25 mg/kg) increased the percentage of maximum possible effect (%MPE) and area under the curve (AUC) of %MPE, indicating an antinociceptive response. Intraperitoneal injection of bicuculline (0.5 and 1 mg/kg) decreased %MPE and AUC of %MPE, suggesting hyperalgesia. Moreover, muscimol by reducing the immobility time of the FST elicited an antidepressant-like response but bicuculline by enhancing the immobility time of the FST caused a depressant-like response. Intracerebroventricular (i.c.v.) microinjection of histamine (5 µg/mouse) enhanced %MPE and AUC of %MPE. i.c.v. infusion of histamine (2.5 and 5 µg/mouse) decreased immobility time in the FST. Co-administration of different doses of histamine along with a sub-threshold dose of muscimol potentiated antinociceptive and antidepressant-like responses produced by histamine. Cotreatment of different doses of histamine plus a noneffective dose of bicuculline reversed antinociception and antidepressant-like effects elicited by histamine. Cotreatment of histamine, muscimol, and bicuculline reversed antinociceptive and antidepressant-like behaviors induced by the drugs. The results demonstrated additive antinociceptive and antidepressant-like effects between histamine and muscimol in mice. In conclusion, our results indicated an interaction between the histaminergic and GABAergic systems in the modulation of pain and depression-like behaviors.
Outcomes of the distal rectal cancer treatment depending on the type of sphincter-sparing surgery
Authors: Gordiichuk Prokip , Gordiichuk Mykola
Published: July 2023

Introduction:

The increase in mid-ampullary and lower ampullary rectal cancer with disappointing treatment results requires ongoing discussion, research, and improvement of the complex treatment.

Materials and methods:

We analyzed the results of complex treatment in 442 patients with stages II–III mid-ampullary and lower ampullary rectal cancer that underwent three types of sphincter-sparing surgeries, including low anterior resection (LAR), intersphincteric resection (ISR), and abdomino-anal resection of the rectum (AAR) at the second stage of complex treatment.

Results:

There was a significant difference between groups in terms of surgery type selection based on the distance from the tumor to the dentate line. When the tumor was located at a distance of 30 mm or less from the dentate line, LAR was performed in 16.4% of cases, whereas ISR and AAR were used in 96.58 and 58.09% of cases, respectively, which is statistically significant (P<0.001). Preventive stoma was used in 78.87% of LAR, 5.9% of ISR, and 6.62% of AAR, which had a significant difference (P<0.001). In the structure of postoperative complications, a group of typical complications (ІІІ–IV) was identified for the types of operations performed. Their frequency when performing LAR was 18.2%, ISR – 7.7%, and AAR – 8.1%, which was statistically significant (P=0.003). The frequency of local recurrences, depending on the type of surgery was not statistically significant (P>0.05), but had a direct correlation with the recurrence-free survival curves. Relapse-free and overall (3 years and 5 years) survival depending on the type of sphincter-preserving surgery did not have a significant difference according to the log-rank test.

Conclusion:

The more types of surgical intervention surgeons have at their disposal, the more rational it is to select the one that will ensure the best treatment results.
The thermodynamic-pathway-determined microstructure evolution of copper under shock compression
Authors: Ling Weidong , Chen Bo , Zhao Zengxiu , Chen Kaiguo , Kang Dongdong , Dai Jiayu
Published: July 2023

Shock-induced structural transformations in copper exhibit notable directional dependence and anisotropy, but the mechanisms that govern the responses of materials with different orientations are not yet well understood. In this study, we employ large-scale non-equilibrium molecular dynamics simulations to investigate the propagation of a shock wave through monocrystal copper and analyse the structural transformation dynamics in detail. Our results indicate that anisotropic structural evolution is determined by the thermodynamic pathway. A shock along the

⟨
100
⟩

orientation causes a rapid and instantaneous temperature spike, resulting in a solid–solid phase transition. Conversely, a liquid metastable state is observed along the

⟨
111
⟩

orientation due to thermodynamic supercooling. Notably, melting still occurs during the

⟨
110
⟩

-oriented shock, even if it falls below the supercooling line in the thermodynamic pathway. These results highlight the importance of considering anisotropy, the thermodynamic pathway and solid-state disordering when interpreting phase transitions induced by shock.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Dynamics of femtosecond heated warm dense copper with time-resolved L3-edge XANES
Authors: Lecherbourg Ludovic , Recoules Vanina , Renaudin Patrick , Dorchies Fabien
Published: July 2023

Combining experimental set up and
ab initio
molecular dynamics simulations, we were able to follow the time evolution of the X-ray absorption near edge spectrum (XANES) of a dense copper plasma. This provides a deep insight into femtosecond laser interaction with a metallic copper target. This paper presents a review of the experimental developments we made to reduce the X-ray probe duration, from approximately 10 ps to fs duration with table-top laser systems. Moreover, we present microscopic scale simulations, performed with Density Functional Theory, as well as macroscopic simulations considering the Two-Temperature Model. These tools allow us to get a complete picture of the evolution of the target at a microscopic level, from the heating process to the melting and expansion stages, with a clear view of the physics involved during these processes.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Simulations of collisional effects in an inner-shell solid-density Mg X-ray laser
Authors: Ren Shenyuan , Vinko Sam , Wark Justin S.
Published: July 2023

Inner-shell

K
α

X-ray lasers have been created by pumping gaseous, solid, and liquid targets with the intense X-ray output of free-electron lasers (FELs). For gaseous targets lasing relies on the creation of

K

-shell core holes on a time-scale short compared with filling via Auger decay. In the case of solid and liquid density systems, collisional effects will also be important, affecting not only populations but also line-widths, both of which impact the degree of overall gain, and its duration. However, to date, such collisional effects have not been extensively studied. We present here initial simulations using the CCFLY code of inner-shell lasing in solid-density Mg, where we self-consistently treat the effects of the incoming FEL radiation and the atomic kinetics of the Mg system, including radiative, Auger and collisional effects. We find that the combination of collisional population of the lower states of the lasing transitions and broadening of the lines precludes lasing on all but the

K
α

of the initially cold system. Even assuming instantaneous turning on of the FEL pump, we find the duration of the gain in the solid system to be sub-femtosecond.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Dynamic properties and the roton mode attenuation in liquid
3
He:
ab initio
study within the self-consistent method of moments
Authors: Filinov A. V. , Ara J. , Tkachenko I. M.
Published: July 2023

The dynamic structure factor and the eigenmodes of density fluctuations in liquid
3
He are studied using a novel non-perturbative approach. This new version of the self-consistent method of moments invokes up to nine sum rules and other exact relations, the two-parameter Shannon information entropy maximization procedure, and the
ab initio
path integral Monte Carlo simulations which provide necessary reliable input information on the system static properties. Detailed analysis is performed of the collective excitations dispersion relations, the modes’ decrements and the static structure factor of
3
He at the saturated vapour pressure. The results are compared to available experimental data by Albergamo
et al.
(Albergamo
et al.
2007
Phys. Rev. Lett.
99
, 205301. (
doi:10.1103/PhysRevLett.99.205301
)) and Fåk
et al.
(Fåk
et al.
1994
J. Low Temp. Phys.
97
, 445–487. (
doi:10.1007/BF00754303
)). The theory reveals a clear signature of the roton-like feature in the particle-hole segment of the excitation spectrum with a significant reduction of the roton decrement in the wavenumber range

1.3
 

Å

−
1

≤
q
≤
2.2
 

Å

−
1

. The observed roton mode remains a well-defined collective mode even in the particle-hole band, where it is strongly damped. The existence of the roton-like mode in the bulk liquid
3
He is confirmed like in other quantum fluids. The phonon branch of the spectrum is in a reasonable agreement with the same experimental data.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Water and foodborne bacterial pathogens isolated from hospitalized children are extensively resistance against commonly used Penicillin-type antibiotics in developing countries
Authors: Awuor Silas Onyango , Omwenga Eric O. , Mariita Richard M. , Musila Jonathan M. , Mbeke Alexander , Musyoka Thommas M.
Published: July 2023

Diarrheal diseases pose a significant threat to children under five years, ranking as the second leading cause of death in this age group. This is partly attributed to the rise of multidrug-resistant enteric bacteria that has further exacerbated the current global health crisis. We herein report a study aimed at identifying common diarrhea-causing bacteria and assessing their antibiotic susceptibility patterns in children under five seeking medical care at Muhoroni County Hospital. Between January and June 2016, a total of 196 under-five children seeking medical care were enrolled with parental or guardian consent. Stool samples were collected and subjected to culture and biochemical tests using standard protocols. Susceptibility testing was performed using conventional antibiotics. Among the participants (196), 125 (63.8%) were from pediatric outpatient departments, while 71 (36.2%) were from pediatric emergency departments. The study population consisted of 105 (53.6%) males and 91 (46.4%) females. Enteric bacterial pathogens were identified in 43 (21.9%) of the samples, with Escherichia coli accounting for 25 (12.8%), Shigella spp. for 11 (5.6%), and Salmonella spp. for 7 (3.6%). All isolated E. coli, Shigella spp., and Salmonella spp. exhibited susceptibility to Ceftriaxone. Notably, 14 (56%) and 13 (52%) of E. coli isolates demonstrated resistance to Amoxicillin and Ampicillin, respectively. The findings provide insights into the distribution of bacteria causing diarrhea in children under five, and associated antibiotic resistance profiles. The investigation highlights an urgent need for effective surveillance on bacterial pathogenicity among children below 5 years, antimicrobial stewardship, and alternative treatment strategies to combat the growing threat of multidrug-resistant enteric bacteria in this vulnerable population.
CRISPR dynamics during the interaction between bacteria and phage in the first year of life
Authors: Wu Jiqiu , Zhang Hanyun , Gan Rui , Xia Yan , Zhang Fan , Wang Daoming , Fu Jingyuan , Barraclough Timothy G.
Published: July 2023

Gut microbiomes in infancy have a profound impact on health in adulthood. CRISPRs play an essential role in the interaction between bacteria and phages. However, the dynamics of CRISPRs in gut microbiomes during early life are poorly understood. In this study, using shotgun metagenomic sequencing data from 82 Swedish infants’ gut microbiomes, 1882 candidate CRISPRs were identified, and their dynamics were analysed. We found large-scale turnover of CRISPRs and their spacers during the first year of life. As well as changes in relative abundance of the bacteria containing CRISPR, acquisition, loss and mutation of spacers were observed within the same CRISPR array sampled over time. Accordingly, the inferred interaction network of bacteria and phage was distinct at different times. This research underpins CRISPR dynamics and their potential role in the interaction between bacteria and phage in early life.
Preclinical and Human Phase 1 Studies of Aerosolized Hydroxychloroquine: Implications for Antiviral COVID-19 Therapy
Authors: Bentur Ohad S. , Hutt Richard , Brassil Donna , Kriegegr Ana C. , Bäckman Per , Charous B. Lauren , Boushey Homer , Gonda Igor , Coller Barry S. , MacArthur Robert B.
Published: July 2023

Based on early reports of the efficacy of hydroxychloroquine sulfate (HCQS) to inhibit SARS-CoV-2 viral replication in vitro, and since severe pulmonary involvement is the major cause of COVID-19 mortality, we assessed the safety and efficacy of aerosolized HCQS (aHCQS) therapy in animals and humans. In a Phase 1 study of aHCQS in healthy volunteers, doses up to 50 mg were well tolerated and estimated epithelial lining fluid concentrations immediately after inhalation (>2,000 μM) exceeded the in vitro concentrations needed for suppression of viral replication (≥119 μM). A study in rats comparing HCQS solution administered orally (13.3 mg/kg) and by intratracheal installation (IT 0.18 mg/kg, <5% of oral dose) demonstrated that at 2 minutes, IT administration was associated with 5X higher mean hydroxychloroquine (HCQ) concentrations in the lung (IT: 49.5 ± 6.5 µg HCQ/g tissue, oral: 9.9 ± 3.4; p<0.01). A subsequent study of IT and intranasal HCQS in the Syrian hamster model of SARS-CoV-2 infection, however, failed to show clinical benefit. We conclude that aHCQS alone is unlikely to be effective for COVID-19, but based on our aHCQS pharmacokinetics and current viral entry data, adding oral HCQS to aHCQS, along with a transmembrane protease inhibitor, may improve efficacy.
Longitudinal multi-omics study reveals common etiology underlying association between plasma proteome and BMI trajectories in adolescent and young adult twins
Authors: Drouard Gabin , Hagenbeek Fiona A. , Whipp Alyce , Pool René , Hottenga Jouke Jan , Jansen Rick , Hubers Nikki , Afonin Aleksei ,   BIOS Consortium,   BBMRI-NL Metabolomics Consortium, Willemsen Gonneke , de Geus Eco J. C. , Ripatti Samuli , Pirinen Matti , Kanninen Katja M. , Boomsma Dorret I. , van Dongen Jenny , Kaprio Jaakko
Published: July 2023

Background

The influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remain underexplored, and the links to other omics in these associations remain to be investigated. We characterized protein-BMI trajectory associations in adolescents and adults and how these connect to other omics layers.

Methods

Our study included two cohorts of longitudinally followed twins: FinnTwin12 (N=651) and the Netherlands Twin Register (NTR) (N=665). Follow-up comprised four BMI measurements over approximately 6 (NTR: 23-27 years old) to 10 years (FinnTwin12: 12-22 years old), with omics data collected at the last BMI measurement. BMI changes were calculated using latent growth curve models. Mixed-effects models were used to quantify the associations between the abundance of 439 plasma proteins with BMI at blood sampling and changes in BMI. The sources of genetic and environmental variation underlying the protein abundances were quantified using twin models, as were the associations of proteins with BMI and BMI changes. In NTR, we investigated the association of gene expression of genes encoding proteins identified in FinnTwin12 with BMI and changes in BMI. We linked identified proteins and their coding genes to plasma metabolites and polygenic risk scores (PRS) using mixed-effect models and correlation networks.

Results

We identified 66 and 14 proteins associated with BMI at blood sampling and changes in BMI, respectively. The average heritability of these proteins was 35%. Of the 66 BMI-protein associations, 43 and 12 showed genetic and environmental correlations, respectively, including 8 proteins showing both. Similarly, we observed 6 and 4 genetic and environmental correlations between changes in BMI and protein abundance, respectively.S100A8gene expression was associated with BMI at blood sampling, and thePRG4andCFIgenes were associated with BMI changes. Proteins showed strong connections with many metabolites and PRSs, but we observed no multi-omics connections among gene expression and other omics layers.

Conclusions

Associations between the proteome and BMI trajectories are characterized by shared genetic, environmental, and metabolic etiologies. We observed few gene-protein pairs associated with BMI or changes in BMI at the proteome and transcriptome levels.
Community Antibiotic Prescribing in Patients with COVID-19 Across Three Pandemic Waves: A Population-Based Cohort Study
Authors: Ciaccio Laura , Donnan Peter T , Parcell Benjamin J , Marwick Charis A
Published: July 2023

Background

Reported changes in antibiotic prescribing during the COVID-19 pandemic have focused on hospital prescribing or community population trends. Community antibiotic prescribing for individuals with COVID-19 are less well described.

Methods

Data covering a complete geographic population (∼800,000) were utilised. SARS-CoV-2 virus test results from February 1, 2020-March 31, 2022 were included. Anonymised data were linked to prescription data +/-28 days of the test, GP data for high-risk comorbidities, and demographic data. Multivariate binary logistic regression examined associations between patient factors and the odds of antibiotic prescription.

Results

Data included 768,206 tests for 184,954 individuals, identifying 16,240 COVID-19 episodes involving 16,025 individuals. There were 3,263 antibiotic prescriptions +/-28 days for 2,385 patients. 35.6% of patients had a prescription only before the test date, 52.5% of patients after, and 11.9% before and after. Antibiotic prescribing reduced over time: 20.4% of episodes in wave one, 17.7% in wave two, and 12.0% in wave three. In multivariate logistic regression, being female (OR 1.31, 95% CI 1.19,1.45), older (OR 3.02, 95% CI 2.50, 3.68 75+ vs <25 years), having a high-risk comorbidity (OR 1.45, 95% CI 1.31, 1.61), a hospital admission +/-28 days of an episode (OR 1.58, 95% CI 1.42, 1.77), and health board region (OR 1.14, 95% CI 1.03, 1.25, board B versus A) increased the odds of receiving an antibiotic.

Conclusion

Community antibiotic prescriptions in COVID-19 episodes were uncommon in this population and likelihood was associated with patient factors. The reduction over pandemic waves may represent increased knowledge regarding COVID-19 treatment and/or evolving symptomatology.
Network analysis of the whole body kinematics in Parkinson diseases following levodopa intake
Authors: Romano Antonella , Liparoti Marianna , Minino Roberta , Polverino Arianna , Cipriano Lorenzo , Ciaramella Francesco , Carotenuto Anna , Tafuri Domenico , Sorrentino Giuseppe , Sorrentino Pierpaolo , Lopez Emahnuel Troisi
Published: July 2023

Background

Three-dimensional motion analysis represents a quantitative and objective approach to assess spatio-temporal and kinematic changes in Parkinson’s disease (PD). However, these parameters, focusing on a specific body segment, provide only segmental information, discarding the complex whole-body patterns underlying the motor impairment. We aimed to assess how levodopa intake affects the whole body, large-scale kinematic network in PD.

Methods

Borrowing from network theory, we used the kinectome framework by calculating the Pearson’s correlation coefficients between the time series acceleration of 21 bone markers. Then, we performed a topological analysis to evaluate the large-scale interactions between body elements. Finally, we performed a multilinear regression analysis in order to verify whether the kinectome’s topological features could predict the clinical variation before and after levodopa intake.

Results

PD patients showed lower nodal strength (i.e., lower synchronization) in the upper body in the medio-lateral acceleration while in on-state with respect to the off state (p-head=0.048; p-C7=0.032; p-T10=0.006). On the contrary, PD patients in on state displayed higher nodal strength (i.e., higher synchronization) of both elbows (right, p=0.002; left, p=0.005), wrists (right, p=0.003; left, p=0.002) and knees (right, p=0.003; left, p=0.039) in the antero-posterior acceleration. Furthermore, the predictive analysis revealed that the nodal strength variations of the arms, following levodopa intake, significantly predicted the clinical variations assessed through the UPDRS-III (R2=0.65; p=0.025).

Conclusions

PD patients in the on-state showed less rigidity during walking, proportional to the UPDRS-III variation. More importantly, we showed that levodopa induces an improvement of the whole body, large-scale kinematic pattern.
Clinical Profile, Comorbidities, and Outcome of the Unvaccinated and Hospitalized for COVID-19 in Northern Brazil: Retrospective Cohort
Authors: Lúcia da Silva Ferreira Ana , Sardinha Daniele Melo , Cristina Viana de Moraes Daiane , Raimunda Rodrigues de Oliveira Maria , Carolina Frazão Viana Mayara , Cristina Oliveira Andrade Natasha , de Nazaré Soares Tamires , José de Paula Souza e Guimarães Ricardo , Nepomuceno Gondim Costa Lima Luana , Valéria Batista Lima Karla
Published: July 2023

Over the course of the pandemic, COVID-19 affected health, the economy and quality of life in Brazil. The worst years for the country were the first and second. There were delays in vaccine purchases for political reasons at the time. The northern region of the country had a higher mortality rate compared to other regions, associated with local vulnerabilities and fragility of surveillance due to geographic and population characteristics. This study aims to investigate the clinical profile, comorbidities, and outcome of unvaccinated people hospitalized for COVID-19 in the state of Pará in 2022. Retrospective cohort epidemiological study, with data from the national epidemiological surveillance of acute and severe respiratory syndromes. Cases reported in 2022 with vaccinated yes or no field and completed doses were included. Only closed cases cure or death were included. We performed a chi-square test on categorical variables and a Mann-Whitney test on numerical variables. We compared vaccinated VS non-vaccinated; we performed the Odds Ratio in the significant variables. We used the SPSS 20.0 software. The study worked with 2,634 cases of COVID-19 hospitalized in the study period, confirmed by RT-PCR (851/32.30%) and (1,784/67.70%) rapid antigen test. The lethality was (778/29.53%), and those vaccinated with two doses were (1,473/55.90%) and those unvaccinated with no dose (1,162/44.10%). Death represents p-<0.001 (HR 1.306 - CI 1.124/1.517) higher risk of the event occurring in the unvaccinated cases, followed by male sex p-0.004 (HR 1.188 - CI 1.058/1.334).. The first cohort in Brazil and in the north of the country to evaluate the clinical profile, comorbidities, and outcome of COVID-19 in hospitalized patients in this Amazon region, which is a region characterized by local vulnerability factors unique to the other regions of Brazil, showed that the unvaccinated were males, younger, with fewer comorbidities, and that they were associated the deaths.
Defining overlooked structures reveals new associations between cortex and cognition in aging and Alzheimer’s disease
Authors: Maboudian Samira A. , Willbrand Ethan H. , Jagust William J. , Weiner Kevin S. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: July 2023

Recent work suggests that indentations of the cerebral cortex, or sulci, may be uniquely vulnerable to atrophy in aging and Alzheimer’s disease (AD) and that posteromedial cortex (PMC) is particularly vulnerable to atrophy and pathology accumulation. However, these studies did not consider small, shallow, and variable tertiary sulci that are located in association cortices and are often associated with human-specific aspects of cognition. Here, we first manually defined 4,362 PMC sulci in 432 hemispheres in 216 participants. Tertiary sulci showed more age- and AD-related thinning than non-tertiary sulci, with the strongest effects for two newly uncovered tertiary sulci. A model-based approach relating sulcal morphology to cognition identified that a subset of these sulci were most associated with memory and executive function scores in older adults. These findings support the retrogenesis hypothesis linking brain development and aging, and provide new neuroanatomical targets for future studies of aging and AD.
Differential Neuroanatomical, Neurochemical, and Behavioral Impacts of Early-Age Isolation in a Eusocial Insect
Authors: Goolsby Billie C. , Smith E. Jordan , Muratore Isabella B. , Coto Zach N. , Muscedere Mario L. , Traniello James F. A.
Published: July 2023

Social experience early in life appears to be necessary for the development of species-typical behavior. Although isolation during critical periods of maturation has been shown to impact behavior by altering gene expression and brain development in invertebrates and vertebrates, workers of some ant species appear resilient to social deprivation and other neurobiological challenges that occur during senescence or due to loss of sensory input. It is unclear if and to what degree neuroanatomy, neurochemistry, and behavior will show deficiencies if social experience in the early adult life of worker ants is compromised. We reared newly-eclosed adult workers of Camponotus floridanus under conditions of social isolation for 2 to 53 days, quantified brain compartment volumes, recorded biogenic amine levels in individual brains, and evaluated movement and behavioral performance to compare the neuroanatomy, neurochemistry, brood-care behavior, and foraging (predatory behavior) of isolated workers with that of workers experiencing natural social contact after adult eclosion. We found that the volume of the antennal lobe, which processes olfactory inputs, was significantly reduced in workers isolated for an average of 40 days, whereas the size of the mushroom bodies, centers of higher-order sensory processing, increased after eclosion and was not significantly different from controls. Titers of the neuromodulators serotonin, dopamine, and octopamine remained stable and were not significantly different in isolation treatments and controls. Brood care, predation, and overall movement were reduced in workers lacking social contact early in life. These results suggest that the behavioral development of isolated workers of C. floridanus is specifically impacted by a reduction in the size of the antennal lobe. Task performance and locomotor ability therefore appear to be sensitive to a loss of social contact through a reduction of olfactory processing ability rather than change in the size of the mushroom bodies, which serve important functions in learning and memory, or the central complex, which controls movement.
Design, construction and optimization of formaldehyde growth biosensors with broad application in Biotechnology
Authors: Schann Karin , Bakker Jenny , Boinot Maximilian , Kuschel Pauline , He Hai , Nattermann Maren , Erb Tobias , Bar-Even Arren , Wenk Sebastian
Published: July 2023

Formaldehyde is a key metabolite in natural and synthetic one-carbon metabolism as well as an important environmental toxin with high toxicity at low concentrations. To engineer efficient formaldehyde producing enzymes and to detect formaldehyde in industrial or environmental samples, it is important to establish highly sensitive, easy to use and affordable formaldehyde detection methods. Here, we transformed the workhorse bacteriumEscherichia coliinto biosensors that can detect a broad range of formaldehyde concentrations. Based on natural and promiscuous formaldehyde assimilation enzymes, we designed and engineered three differentE. colistrains that depend on formaldehyde assimilation for cellular growth. After in depth characterization of these biosensors, we show that the formaldehyde sensitivity can be improved through adaptive laboratory evolution or modification of metabolic branch points. The metabolic engineering strategy presented in this work allowed the creation ofE. colibiosensors that can detect formaldehyde in a concentration range from ∼30 μM to ∼13 mM. Using the most sensitive strain, we benchmarked thein vivoactivities of different, widely used NAD-dependent methanol dehydrogenases, the rate-limiting enzyme in synthetic methylotrophy. We also show that the strains can grow upon external addition of formaldehyde indicating their potential use for applications beyond enzyme engineering. The formaldehyde biosensors developed in this study are fully genomic and can be used as plug and play devices for screening large enzyme libraries. Thus, they have the potential to greatly advance enzyme engineering and might even be used for environmental monitoring or analysis of industrial probes.

Highlights

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Conversion ofE. coliinto three different formaldehyde growth biosensors

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Biosensors are fully genomic and grow robustly when formaldehyde is present

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Biosensors can detect formaldehyde concentrations ranging from ∼30 μM to ∼13 mM

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Benchmarking of biotechnological relevant methanol dehydrogenases reveals potential of biosensors for enzyme engineering

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Biosensors grow upon direct addition of formaldehyde indicating potential use in environmental or industrial settings
Exhaustive identification of genome-wide binding events of transcriptional regulators with ICEBERG
Authors: Nordin Anna , Pagella Pierfrancesco , Zambanini Gianluca , Cantù Claudio
Published: July 2023

Genome-wide protein interaction assays aspire to map the complete binding pattern of gene regulators. How-ever, common practice relies on replication and high stringency statistics which favor false negatives over false positives, thereby excluding portions of signal which may represent biologically relevant events. Here, we present ICEBERG (Increased Capture of Enrichment By Exhaustive Replicate aGgregation), an experimental and analytical pipeline that harnesses large numbers of CUT&RUN replicates to discover the full set of binding events and chart the line between false positives and false negatives. We employed ICEBERG to map the full set of H3K4me3-marked regulatory regions and β-catenin targets in human colorectal cancer cells. The ICE-BERG datasets allow benchmarking of individual replicates, comparison of the performance of peak calling and replication approaches and expose the arbitrary nature of other strategies to identify reproducible peaks. Instead of a static view of genomic targets, ICEBERG established a spectrum of detection probabilities across the genome for a given factor, underlying the intrinsic dynamicity of its mechanism of action, and permitting to distinguish frequent from rare regulation events. Finally, ICEBERG discovered instances, undetectable with other approaches, that might underlie novel mechanisms of colorectal cancer progression.
Diagnosis of planktonic trophic network dynamics with sharp qualitative changes
Authors: Gaucherel Cedric , Fayolle Stolian , Savelli Raphael , Philippine Olivier , Pommereau Franck , Dupuy Christine
Published: July 2023

Abstract

Trophic interaction networks are notoriously difficult to understand and to diagnose (i.e., to identify contrasted network functioning regimes). Such ecological networks have many direct and indirect connections between species, and these connections are not static but often vary over time. These topological changes, as opposed to a dynamic on a static (frozen) network, can be triggered by natural forcings (e.g., seasons) and/or by human influences (e.g., nutrient or pollution inputs). Aquatic trophic networks are especially dynamic and versatile, thus suggesting new approaches for identifying network structures and functioning in a comprehensive manner.

In this study, a qualitative model was devised for this purpose. Applying discrete-event models from theoretical computer science, a mechanistic and qualitative model was developed that allowed computation of the exhaustive dynamics of a given trophic network and its environment. Once the model definition is assumed, it provides all possible trajectories of the network from a chosen initial state. In a rigorous and analytical approach, for the first time, we validated the model on one theoretical and two observed trajectories recorded at freshwater stations in the La Rochelle region (Western France). The model appears to be easy to build and intuitive, and it provides additional relevant trajectories to the expert community. We hope this formal approach will open a new avenue in identifying and predicting trophic (and non-trophic) ecological networks.
Decoupled evolution of theSex Peptidegene family andSex Peptide ReceptorinDrosophilidae
Authors: Hopkins Ben R. , Angus-Henry Aidan , Kim Bernard Y. , Carlisle Jolie A. , Thompson Ammon , Kopp Artyom
Published: July 2023

Across internally fertilising species, males transfer ejaculate proteins that trigger wide-ranging changes in female behaviour and physiology. Much theory has been developed to explore the drivers of ejaculate protein evolution. The accelerating availability of high-quality genomes now allows us to test how these proteins are evolving at fine taxonomic scales. Here, we use genomes from 264 species to chart the evolutionary history of Sex Peptide (SP), a potent regulator of female post-mating responses inDrosophila melanogaster. We infer thatSPfirst evolved in theDrosophilinaesubfamily and has followed markedly different evolutionary trajectories in different lineages. Outside of theSophophora-Lordiphosa,SPexists largely as a single-copy gene with independent losses in several lineages. Within theSophophora-Lordiphosa,theSPgene family has repeatedly and independently expanded. Up to seven copies, collectively displaying extensive sequence variation, are present in some species. Despite these changes,SPexpression remains restricted to the male reproductive tract. Alongside, we document considerable interspecific variation in the presence and morphology of seminal microcarriers that, despite the critical role SP plays in microcarrier assembly inD. melanogaster, appear to be independent of changes in the presence/absence or sequence of SP. We end by providing evidence that SP’s evolution is decoupled from that of its receptor, SPR, in which we detect no evidence of correlated diversifying selection. Collectively, our work describes the divergent evolutionary trajectories that a novel gene has taken following its origin and finds a surprisingly weak coevolutionary signal between a supposedly sexually antagonistic protein and its receptor.

Significance

In insects, seminal fluid proteins (SFPs) induce dramatic changes in female behaviour and physiology. How this degree of male influence evolves remains a central question in sexual selection research. Here, we map the origin and diversification of the posterchild insect SFP, theDrosophilaSex Peptide (SP), across 264 Diptera species. We show thatSPfirst evolved at the base of the subfamilyDrosophilinaeand followed markedly different evolutionary trajectories in different lineages, including accelerated change in sequence, copy number, and genomic position in the lineage leading toD. melanogaster.By contrast, we find only limited, uncorrelated change in the sequence of its receptor, SPR, arguing against a sexually antagonistic coevolutionary arms race between these loci on macroevolutionary time scales.
Exploring the Potential of Large Language Models in Personalized Diabetes Treatment Strategies
Authors: Yang Hao , Li Jiaxi , Liu Siru , Du Lei , Liu Xiali , Huang Yong , Shi Qingke , Liu Jialin
Published: July 2023

This study aims to explore the application of a fine-tuned model-based outpatient treatment support system for the treatment of patients with diabetes, and evaluate its effectiveness and potential value.

Methods

The ChatGLM model was selected as the subject of investigation and trained using the P-tuning and LoRA fine-tuning methods. Subsequently, the fine-tuned model was successfully integrated into the Hospital Information System (HIS). The system generates personalized treatment recommendations, laboratory test suggestions, and medication prompts based on patients’ basic information, chief complaints, medical history, and diagnosis data.

Results

Experimental testing revealed that the fine-tuned ChatGLM model is capable of generating accurate treatment recommendations based on patient information, while providing appropriate laboratory test suggestions and medication prompts. However, for patients with complex medical records, the model’s outputs may carry certain risks and cannot fully substitute outpatient physicians’ clinical judgment and decision-making abilities. The model’s input data is confined to electronic health record (EHR), limiting the ability to comprehensively reconstruct the patient’s treatment process and occasionally leading to misjudgments of the patient’s treatment goals.

Conclusion

This study demonstrates the potential of the fine-tuned ChatGLM model in assisting the treatment of patients with diabetes, providing reference recommendations to healthcare professionals to enhance work efficiency and quality. However, further improvements and optimizations are still required, particularly regarding medication therapy and the model’s adaptability.
Time is of the essence: A general framework for uncovering temporal structures of communities
Authors: Yin Hannah , Rudolf Volker H. W.
Published: July 2023

Ecological communities are inherently dynamic: species constantly turn over within years, months, weeks, or even days. These temporal shifts in community composition determine essential aspects of species interactions and how energy, nutrients, information, diseases, and perturbations "flow" through systems. Yet, our understanding of community structure has relied heavily on static analyses not designed to capture critical features of this dynamic temporal dimension of communities. Here, we propose a conceptual and methodological framework for quantifying and analyzing this temporal dimension. Conceptually, we split the temporal structure into two definitive features, sequence and duration, and review how they are linked to key concepts in ecology. We then outline how we can capture these definitive features using perspectives and tools from temporal graph theory. We demonstrate how we can easily integrate ongoing research on phenology into this framework and highlight what new opportunities arise from this approach to answer fundamental questions in community ecology. As climate change reshuffles ecological communities worldwide, quantifying the temporal organization of communities is imperative to resolve the fundamental processes that shape natural ecosystems and predict how these systems may change in the future.
Uncovering novel roles of miR-122 in the pathophysiology of the liver: Potential interaction with NRF1 and E2F4 signaling
Authors: Paluschinski Martha , Schira-Heinen Jessica , Pellegrino Rossella , Heij Lara R. , Bednarsch Jan , Neumann Ulf P. , Longerich Thomas , Stuehler Kai , Luedde Tom , Castoldi Mirco
Published: July 2023

MicroRNA miR-122 plays a pivotal role in liver function. Despite numerous studies investigating this miRNA, the global network of genes regulated by miR-122 and its contribution to the underlying pathophysiological mechanisms remain largely unknown. To gain a deeper understanding of miR-122 activity, we employed two complementary approaches. Firstly, through transcriptome analysis of polyribosome-bound RNAs, we discovered that miR-122 exhibits potential antagonistic effects on specific transcription factors known to be dysregulated in liver disease, including nuclear respiratory factor-1 (NRF1) and the E2F Transcription Factor 4 (E2F4). Secondly, through proteome analysis of hepatoma cell transfected with either miR-122 mimic or antagomiR we discovered changes in several proteins associated with increased malignancy. Interestingly, many of these proteins were reported to be transcriptionally regulated by NRF1 and E2F4, six of which we validated as miR-122 targets. Among these, a negative correlation was observed between miR-122 and glucose-6-phosphate dehydrogenase levels in the livers of patients with hepatitis B virus-associated hepatocellular carcinoma. This study provides novel insights into potential alterations of molecular pathway occurring at the early stages of liver disease, driven by the dysregulation of miR-122 and its associated genes.