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Purpose To investigate the possible risk factors for treatment failure in patients who had undergone Preserflo Microshunt (PMS) implantation, using anterior-segment optical coherence tomography (AS-OCT) to analyze the internal structures of the bleb. Methods The PMS blebs of 54 patients were evaluated with AS-OCT. A mathematical model was used to calculate the total filtering surface of the episcleral fluid cavity (EFC) and the hydraulic conductivity (HC) of the bleb wall. Complete and qualified success were defined as IOP between 6 and 17 mmHg with or without glaucoma medication. The relation between baseline characteristics and probability of bleb success was analyzed by bivariate and multivariate logistic regression. The main outcome measures were mean bleb wall thickness (BWT), reflectivity (BWR), HC, mean horizontal and vertical diameter and total filtering surface (TFS) of the EFC. Results Blebs from 74% patients were considered as complete success and 26% as failure. BWR and BWT increased linearly up to the first year in both groups. BWR was higher in the group failure (p = 0.02) and BWT in the group success (pConclusions AS-OCT revealed that successful PMS blebs could show either thick hyporreflective walls or wide filtering surfaces with thin capsules. A higher baseline IOP increased the probability of surgical success.

Background As the European population with Spinal Cord Injury (SCI) is expected to become older, a better understanding of ageing with SCI using functioning, the health indicator used to model healthy ageing trajectories, is needed. We aimed to describe patterns of functioning in SCI by chronological age, age at injury and time since injury across eleven European countries using a common functioning metric, and to identify country-specific environmental determinants of functioning. Methods Data from 6’635 participants of the International Spinal Cord Injury Community Survey was used. The hierarchical version of Generalized Partial Credit Model, casted in a Bayesian framework, was used to create a common functioning metric and overall scores. For each country, linear regression was used to investigate associations between functioning, chronological age, age at SCI or time since injury for persons with para- and tetraplegia. Multiple linear regression and the proportional marginal variance decomposition technique were used to identify environmental determinants. Results In countries with representative samples older chronological age was consistently associated with a decline in functioning for paraplegia but not for tetraplegia. Age at injury and functioning level were associated, but patterns differed across countries. An association between time since injury and functioning was not observed in most countries, neither for paraplegia nor for tetraplegia. Problems with the accessibility of homes of friends and relatives, access to public places and long-distance transportation were consistently key determinants of functioning. Conclusions Functioning is a key health indicator and the fundament of ageing research. Enhancing methods traditionally used to develop metrics with Bayesian approach, we were able to create a common metric of functioning with cardinal properties and to estimate overall scores comparable across countries. Focusing on functioning, our study complements epidemiological evidence on SCI-specific mortality and morbidity in Europe and identify initial targets for evidence-informed policy-making.

While Misiones, Argentina contains one of the largest remnants of Upper Paraná Atlantic Forest ecoregion, one of the world’s biodiversity hotspots, only ~50% of this native forest is protected. Each protected area is at risk of becoming an island of native forest surrounded by a matrix of altered habitats due to ongoing land conversion. In an effort to maximize long-term connectivity between existing protected areas, DeMatteo [1] used a multifaceted cost analysis to determine the optimal location for the region’s first multispecies corridor using noninvasive data on jaguars (Panthera onca), pumas (Puma concolor), ocelots (Leopardus pardalis), southern tiger cats (Leopardus guttulus), and bush dogs (Speothos venaticus). This work builds on this framework by integrating new field data that broadens the scope of species-specific data across the region’s heterogeneous landscape, which varies in vegetation, disturbance, human proximity, and protective status. In addition, two different land use layers are compared across the distributions of the five carnivores, the overlap in their independent distributions, and their relationship to the multispecies corridor. Interpretation of these land use data to species-specific habitat suitability goes beyond DeMatteo [1], with a subdivision of suitability into marginal and optimal areas. This refined scale allows a reanalysis of key areas in the multispecies corridor, where connectivity was previously defined as at highly-at-risk, allowing for a more directed development of management strategies. These analyses and their interpretation extend beyond northern-central Misiones, as the threats are not unique to this region. The need to develop management strategies that balance human-wildlife needs will continue to grow as humans expand their footprint. The techniques applied in this analysis provide a way to identify key areas that require specific management strategies, either through restoration, protection, or a combination of both.

Background Few studies have analyzed the relationship between glucose variability (GV) and adverse health outcomes in patients with differences in glycemic status. The present study tests the hypothesis that GV predicts all-cause mortality regardless of glycemic status after simple adjustment (age and sex) and full adjustment (age, sex, cardiovascular disease, hypertension, use of aspirin, statins, GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors, baseline FPG and average HbA1c). Methods Prospective cohort study with 795 normoglycemic patients, 233 patients with prediabetes, and 4,102 patients with type 2 diabetes. GV was measured using the coefficient of variation of fasting plasma glucose (CV-FPG) over 12 years of follow-up. The outcome measure was all-cause mortality. Results A total of 1,223 patients (657 men, 566 women) died after a median of 9.8 years of follow-up, with an all-cause mortality rate of 23.35/1,000 person-years. In prediabetes or T2DM patients, the fourth quartile of CV-FPG exerted a significant effect on all-cause mortality after simple and full adjustment. A sensitivity analysis excluding participants who died during the first year of follow-up revealed the following results for the highest quartile in the fully adjusted model: overall, HR (95%CI) = 1.54 (1.26–1.89); dysglycemia (prediabetes and T2DM), HR = 1.41 (1.15–1.73); T2DM, HR = 1.36 (1.10–1.67). Conclusion We found CV-FPG to be useful for measurement of GV. It could also be used for the prognostic stratification of patients with dysglycemia.

Background During follow-up, patients severely affected by coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation (IMV), show symptoms of Post-Intensive Care Syndrome (PICS) such as cognitive impairment, psychological disability, and neuromuscular deconditioning. In COVID-19 pandemic, it is a priority to develop multidisciplinary post-acute care services to address the long-term multisystemic impact of COVID-19. Research question Which are the most relevant multisystemic sequelae in severe post-COVID-19 patients? Study design and methods Observational chart review study that included adult patients discharged from a referral hospital for respiratory diseases in Mexico after recovering from severe COVID-19 disease from December 23, 2020, to April 24, 2021. Data were collected from 280 of 612 potentially eligible patients to evaluate persistent symptoms and compare sequelae in patients who required intubation, using a standardized questionnaire of symptoms, in addition to findings reported during the face-to-face health assessment. Univariable and multivariate analyses were performed for the association among the requirement of IMV and the long-term persistence of symptoms. Results 280 patients were included. The median age was 55 (range, 19 to 86) years, and 152 (54.3%) were men. The mean length of hospital stay was 19 (SD, 14.1) days. During hospitalization 168 (60%) participants received IMV. A large proportion of these patients reported fatigue (38.7%), paresthesia (35.1%), dyspnea (32.7%) and headache (28%); meanwhile only 3 (1.8%) of them were asymptomatic. Patients who required intubation were more likely to have neuropsychiatric (67.3% vs 55.4%; OR, 1.79 [95% CI, 1.08 to 2.97]) and musculoskeletal involvement (38.7% vs. 25.9%; OR, 1.92 [95% CI, 1.12 to 3.27]), adjusted for age,sex and hospitalization time. Interpretation The proportion of patients requiring intubation was 60%, reporting persistent symptoms in 98% of them. Neuropsychiatric and musculoskeletal symptoms were the most predominant symptoms in these patients, with a significant difference. Post-COVID-19 syndrome is a frequent problem in patients who required IVM. Physicians in ICU and in care of COVID-19 patients should be aware of this syndrome in order to avoid more complications.

Next-Generation Sequencing (NGS) is widely used to investigate genomic variation. In several studies, the genetic variation of Mycobacterium tuberculosis has been analyzed in sputum samples without previous culture, using target enrichment methodologies for NGS. Alignments obtained by different programs generally map the sequences under default parameters, and from these results, it is assumed that only Mycobacterium reads will be obtained. However, variants of interest microorganism in clinical samples can be confused with a vast collection of reads from other bacteria, viruses, and human DNA. Currently, there are no standardized pipelines, and the cleaning success is never verified since there is a lack of rigorous controls to identify and remove reads from other sputum-microorganisms genetically similar to M. tuberculosis. Therefore, we designed a bioinformatic pipeline to process NGS data from sputum samples, including several filters and quality control points to identify and eliminate non-M. tuberculosis reads to obtain a reliable genetic variant report. Our proposal uses the SURPI software as a taxonomic classifier to filter input sequences and perform a mapping that provides the highest percentage of Mycobacterium reads, minimizing the reads from other microorganisms. We then use the filtered sequences to perform variant calling with the GATK software, ensuring the mapping quality, realignment, recalibration, hard-filtering, and post-filter to increase the reliability of the reported variants. Using default mapping parameters, we identified reads of contaminant bacteria, such as Streptococcus, Rhotia, Actinomyces, and Veillonella. Our final mapping strategy allowed a sequence identity of 97.8% between the input reads and the whole M. tuberculosis reference genome H37Rv using a genomic edit distance of three, thus removing 98.8% of the off-target sequences with a Mycobacterium reads loss of 1.7%. Finally, more than 200 unreliable genetic variants were removed during the variant calling, increasing the report’s reliability.

Background High-quality data on time of stroke onset and time of hospital arrival is required for proper evaluation of points of delay that might hinder access to medical care after the onset of stroke symptoms. Purpose Based on (SITS Dataset) in Egyptian stroke patients, we aimed to explore factors related to time of onset versus time of hospital arrival for acute ischemic stroke (AIS). Material and methods We included 1,450 AIS patients from two stroke centers of Ain Shams University, Cairo, Egypt. We divided the day to four quarters and evaluated relationship between different factors and time of stroke onset and time of hospital arrival. The factors included: age, sex, duration from stroke onset to hospital arrival, type of management, type of stroke (TOAST classification), National Institute of Health Stroke Scale (NIHSS) on admission and favorable outcome modified Rankin Scale (mRS ≤2). Results Pre-hospital: highest stroke incidence was in the first and fourth quarters. There was no significant difference in the mean age, sex, type of stroke in relation to time of onset. NIHSS was significantly less in onset in third quarter of the day. Percentage of patients who received thrombolytic therapy was higher with onset in the first 2 quarters of the day (p =

BACKGROUND: The COVID-19 pandemic has caused over 68.7 million infections and 1.35 million deaths in South America. There are limited data on SARS-CoV-2 seropositivity and its determinants from Andean countries prior to mass vaccinations against COVID-19. OBJECTIVE: To estimate SARS-CoV-2 seropositivity and its determinants before vaccination in occupational groups of adults presumed to have different levels of exposure and associations with potential symptomatology. METHODS: We measured seropositivity of anti-SARS-CoV-2 IgG antibodies in a cross-sectional study of vaccine-naïve adults aged 18 years and older, recruited within three occupational risk groups (defined as low [LR], moderate [MR], and high [HR]) between January and September 2021 in two Andean cities in Ecuador. Associations with risk factors were estimated using logistic regression. RESULTS: In a sample of 882 adults, IgG seropositivity for the three different occupational risk groups was 39.9% (CI 95% 35.3-44.6), 74.6% (CI 95% 66.4-81.4), and 39.0% (CI 95% 34.0-44.4) for the HR, MR, and LR groups, respectively. History of an illness with loss of taste and/or smell was significantly associated with seropositivity in all occupational groups, with adjusted ORs of 14.31 (95%CI, 5.83-35.12; p

BackgroundAs global populations age, cross-national comparisons of cognitive health and dementia risk are increasingly valuable. It remains unclear, however, whether country-level differences in cognitive function are attributable to population differences or bias due to incommensurate measurement. To demonstrate an effective method for cross-national comparison studies, we aimed to statistically harmonize measures of episodic memory and language function across two population-based cohorts of older adults in the United States (HRS HCAP) and India (LASI-DAD).MethodsData for 3,496 HRS HCAP (≥65 years) and 3,152 LASI-DAD (≥60 years) participants were statistically harmonized for episodic memory and language performance using confirmatory factor analysis (CFA) methods. Episodic memory and language factor variables were investigated for differential item functioning (DIF) and precision.ResultsCFA models estimating episodic memory and language domains based on a priori adjudication of comparable items fit the data well. DIF analyses revealed that four out of ten episodic memory items and five out of twelve language items measured the underlying construct comparably across samples. DIF-modified episodic memory and language factor scores showed comparable patterns of precision across the range of the latent trait for each sample.ConclusionsHarmonization of cognitive measures will facilitate future investigation of cross-national differences in cognitive performance and differential effects of risk factors, policies, and treatments, reducing study-level measurement and administrative influences. As international aging studies become more widely available, advanced statistical methods such as those described in this study will become increasingly central to making universal generalizations and drawing valid conclusions about cognitive aging of the global population.

BackgroundThere is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals.MethodsWe analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

BACKGROUND: The rotational activation created by spiral waves may be a mechanism for atrial fibrillation (AF), yet it is unclear how activation patterns obtained from endocardial baskets are influenced by the 3D geometric curvature of the atrium or unfolding into 2D maps. We develop algorithms that can visualize spiral waves and their tip locations on curved atrial geometries. We use these algorithms to quantify differences in AF maps and spiral tip locations between 3D basket reconstructions, projection onto 3D anatomical shells and unfolded 2D surfaces. METHODS: We tested our algorithms in N = 20 patients in whom AF was recorded from 64-pole baskets (Abbott, CA). Phase maps were generated by non-proprietary software to identify the tips of spiral waves, indicated by phase singularities. The number and density of spiral tips were compared in patient-specific 3D shells constructed from the basket, as well as 3D maps from clinical electroanatomic mapping systems and 2D maps. RESULTS: Patients (59.4±12.7 yrs, 60% M) showed 1.7±0.8 phase singularities/patient, in whom ablation terminated AF in 11/20 patients (55%). There was no difference in the location of phase singularities, between 3D curved surfaces and 2D unfolded surfaces, with a median correlation coefficient between phase singularity density maps of 0.985 (0.978-0.990). No significant impact was noted by phase singularities location in more curved regions or relative to the basket location (p>0.1). CONCLUSIONS: AF maps and phase singularities mapped by endocardial baskets are qualitatively and quantitatively similar whether calculated by 3D phase maps on patient-specific curved atrial geometries or in 2D. Phase maps on patient-specific geometries may be easier to interpret relative to critical structures for ablation planning.

Using Twitter to implement public health awareness campaigns is on the rise, but campaign monitoring and evaluation are largely dependent on basic Twitter Analytics. To establish the potential of social network theory-based metrics in better understanding public health campaigns, we analyzed real-time user interactions on Twitter during the 2020 World Breastfeeding Week (WBW) as an exemplar case. Social network analysis (SNA), including community and influencer identification, as well as topic modeling were used to compare the activity of n = 29,958 campaign participants and n = 10,694 reference users from the six-months pre-campaign period. Users formed more inter-connected relationships during the campaign, retweeting and mentioning each other 46,161 times compared to 10,662 times in the prior six months. Campaign participants formed identifiable communities that were not only based on their geolocation, but also based on interests and professional background. While influencers who dominated the WBW conversations were disproportionally members of the scientific community, the campaign did mobilize influencers from the general public who seemed to play a "bridging" role between the public and the scientific community. Users communicated about the campaign beyond its original themes to also discuss breastfeeding within the context of social and racial inequities. Applying SNA allowed understanding of the breastfeeding campaign's messaging and engagement dynamics across communities and influencers. Moving forward, WBW could benefit from improving targeting to enhance geographic coverage and user interactions. As this exemplar case indicates, social network theory and analysis can be used to inform other public health campaigns with data on user interactions that go beyond traditional metrics.

The aim of this work was to use TOPAS Monte Carlo simulations to model the effect of magnetic fields on dose distributions in brachytherapy lung treatments, under ideal and clinical conditions. Idealistic studies were modeled consisting of either a monoenergetic electron source of 432 keV, or a polyenergetic electron source using the spectrum of secondary electrons produced by 192Ir gamma-ray irradiation. The electron source was positioned in the center of a homogeneous, lung tissue phantom (ρ = 0.26 g/cm3). Conversely, the clinical study was simulated using the VariSource VS2000 192Ir source in a patient with a lung tumor. Three contoured volumes were considered: the tumor, the planning tumor volume (PTV), and the lung. In all studies, dose distributions were calculated in the presence or absence of a constant magnetic field of 3T. Also, TG-43 parameters were calculated for the VariSource and compared with published data from EGS-brachy (EGSnrc) and PENELOPE. The magnetic field affected the dose distributions in the idealistic studies. For the monoenergetic and poly-energetic studies, the radial distance of the 10% iso-dose line was reduced in the presence of the magnetic field by 64.9% and 24.6%, respectively. For the clinical study, the magnetic field caused differences of 10% on average in the patient dose distributions. Nevertheless, differences in dose-volume histograms were below 2%. Finally, for TG-43 parameters, the dose-rate constant from TOPAS differed by 0.09% ± 0.33% and 0.18% ± 0.33% with respect to EGS-brachy and PENELOPE, respectively. The geometry and anisotropy functions differed within 1.2% ± 1.1%, and within 0.0% ± 0.3%, respectively. The Lorentz forces inside a 3T magnetic resonance machine during 192Ir brachytherapy treatment of the lung are not large enough to affect the tumor dose distributions significantly, as expected. Nevertheless, large local differences were found in the lung tissue. Applications of this effect are therefore limited by the fact that meaningful differences appeared only in regions containing air, which is not abundant inside the human.

Ion channels have recently attracted attention as potential mediators of skin disease. Here, we explored the consequences of genetically encoded induction of the cell volume-regulating Ca2+-activated KCa3.1 channel (Kcnn4) for murine epidermal homeostasis. Doxycycline-treated mice harboring the KCa3.1+-transgene under the control of the reverse tetracycline-sensitive transactivator (rtTA) showed 800-fold channel overexpression above basal levels in the skin and solid KCa3.1-currents in keratinocytes. This overexpression resulted in epidermal spongiosis, progressive epidermal hyperplasia and hyperkeratosis, itch and ulcers. The condition was accompanied by production of the pro-proliferative and pro-inflammatory cytokines, IL-β1 (60-fold), IL-6 (33-fold), and TNFα (26-fold) in the skin. Treatment of mice with the KCa3.1-selective blocker, Senicapoc, significantly suppressed spongiosis and hyperplasia, as well as induction of IL-β1 (-88%) and IL-6 (-90%). In conclusion, KCa3.1-induction in the epidermis caused expression of pro-proliferative cytokines leading to spongiosis, hyperplasia and hyperkeratosis. This skin condition resembles pathological features of eczematous dermatitis and identifies KCa3.1 as a regulator of epidermal homeostasis and spongiosis, and as a potential therapeutic target.

Breastfeeding is one of many health practices known to support the survival and health of mother and infant, yet low breastfeeding rates persist globally. These rates may be influenced by limited diffusion of evidence-based research and guidelines from the scientific community (SC). As recently highlighted by the National Academy of Sciences, there is a need for the SC to diffuse its findings to the public more effectively online, as means to counteract the spread of misinformation. In response to this call, we gathered data from Twitter for one month from major breastfeeding hashtags resulting in an interconnected social network (n = 3,798 users). We then identified 59 influencers who disproportionately influenced information flow using social network analysis. These influencers were from the SC (e.g. academics, researchers, health care practitioners), as well as interested citizens (IC) and companies. We then conducted an ego-network analysis of influencer networks, developed ego maps, and compared diffusion metrics across the SC, IC and company influencers. We also qualitatively analyzed their tweets (n = 711) to understand the type of information being diffused. SC influencers were the least efficient communicators. Although having the highest tweeting activity (80% of tweets), they did not reach more individuals compared to IC and companies (two-step ego size: 220± 99, 188 ± 124, 169 ± 97 respectively, P = 0.28). Content analysis of tweets suggest IC are more active than the SC in diffusing evidence-based breastfeeding knowledge, with 35% of their tweets around recent research findings compared to only 12% by the SC. Nonetheless, in terms of outreach to the general public, the two-step networks of SC influences were more heterogenous than ICs (55.7 ± 5.07, 50.9 ± 12.0, respectively, P

Invasive alien species are a major threat to native insular species. Eradicating invasive mammals from islands is a feasible and proven approach to prevent biodiversity loss. We developed a conceptual framework to identify globally important islands for invasive mammal eradications to prevent imminent extinctions of highly threatened species using biogeographic and technical factors, plus a novel approach to consider socio-political feasibility. We applied this framework using a comprehensive dataset describing the distribution of 1,184 highly threatened native vertebrate species (i.e. those listed as Critically Endangered or Endangered on the IUCN Red List) and 184 non-native mammals on 1,279 islands worldwide. Based on extinction risk, irreplaceability, severity of impact from invasive species, and technical feasibility of eradication, we identified and ranked 292 of the most important islands where eradicating invasive mammals would benefit highly threatened vertebrates. When socio-political feasibility was considered, we identified 169 of these islands where eradication planning or operation could be initiated by 2020 or 2030 and would improve the survival prospects of 9.4% of the Earths most highly threatened terrestrial insular vertebrates (111 of 1,184 species). Of these, 107 islands were in 34 countries and territories and could have eradication projects initiated by 2020. Concentrating efforts to eradicate invasive mammals on these 107 islands would benefit 151 populations of 80 highly threatened vertebrates and make a major contribution towards achieving global conservation targets adopted by the worlds nations.

Climate change is driving shifts in the abundance and distribution of marine fish and invertebrates and is having direct and indirect impacts on seafood catches and fishing communities, exacerbating the already negative effects of unsustainably high fishing pressure that exist for some stocks. Although the majority of fisheries in the world are managed at the national or local scale, most existing approaches to assessing climate impacts on fisheries have been developed on a global scale. It is often difficult to translate from the global to regional and local settings because of limited relevant data. To address the need for fisheries management entities to identify those fisheries with the greatest potential for climate change impacts, we present an approach for estimating expected climate change-driven impacts on the productivity and spatial range of fisheries at the regional scale in a data-poor context. We use a set of representative Mexican fisheries as test cases. To assess the implications of climate impacts, we compare biomass, harvest, and profit outcomes from a bioeconomic model under contrasting management policies and with and without climate change. Overall results show that climate change is estimated to negatively affect nearly every fishery in our study. However, the results indicate that overfishing is a greater threat than climate change for these fisheries, hence fixing current management challenges has a greater upside than the projected future costs of moderate levels of climate change. Additionally, this study provides meaningful first approximations of potential effects of both climate change and management reform in Mexican fisheries. Using the climate impact estimations and model outputs, we identify high priority stocks, fleets, and regions for policy reform in Mexico in the face of climate change. This approach can be applied in other data-poor circumstances to focus future research and policy reform efforts on stocks now subject to additional stress due to climate change. Considering their growing relevance as a critical source of protein and micronutrients to nourish our growing population, it is urgent for regions to develop sound fishery management policies in the short-term as they are the most important intervention to mitigate the adverse effects of climate change on marine fisheries.

This study estimates the effect of data sharing on the citations of academic articles, using journal policies as a natural experiment. We begin by examining 17 high-impact journals that have adopted the requirement that data from published articles be publicly posted. We match these 17 journals to 13 journals without policy changes and find that empirical articles published just before their change in editorial policy have citation rates with no statistically significant difference from those published shortly after the shift. We then ask whether this null result stems from poor compliance with data sharing policies, and use the data sharing policy changes as instrumental variables to examine more closely two leading journals in economics and political science with relatively strong enforcement of new data policies. We find that articles that make their data available receive 97 additional citations (estimate standard error of 34). We conclude that: a) authors who share data may be rewarded eventually with additional scholarly citations, and b) data-posting policies alone do not increase the impact of articles published in a journal unless those policies are enforced.

Pseudomonas aeruginosa is an opportunist bacterium that causes acute and chronic infections. During acute infections, the type III secretion system (T3SS) plays a pivotal role in allowing the bacteria to translocate effectors such as ExoS, ExoT, and ExoY into host cells for colonization. Previous research on the involvement of quorum sensing systems Las and Rhl in controlling the T3SS gene expression produced ambiguous results. In this study, we determined the role of the Las and Rhl systems and the PqsE protein on T3SS expression. Our results show that in the wild-type PAO1 strain, the deletion of lasR or pqsE do not affect the secretion of ExoS. However, rhlI inactivation increases the expression of T3SS genes. In contrast to the rhlI deletion, rhlR inactivation decreases both T3SS genes expression and ExoS secreted protein levels, and this phenotype is restored when this mutant is complemented with the exsA gene, which codes for the master regulator of the T3SS. Additionally, cytotoxicity is affected in the rhlR mutant strain compared with its PAO1 parental strain. Overall, our results indicate that neither the Las system nor PqsE are involved in regulating the T3SS. Moreover, the Rhl system components have opposite effects, RhlI participates in negatively controlling the T3SS expression, while RhlR does it in a positive way, and this regulation is independent of C4 or PqsE. Finally, we show that rhlR, rhlI, or pqsE inactivation abolished pyocyanin production in T3SS-induction conditions. The ability of RhlR to act as a positive T3SS regulator in the absence of its cognate autoinducer and PqsE shows that it is a versatile regulator that controls different virulence traits allowing P. aeruginosa to compete for a niche. [ABSTRACT FROM AUTHOR]

The main objective of this study is to determine whether the employment of fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC; and Phesgo as brand name) to treat metastatic HER2-positive breast cancer patients would minimize costs compared to the traditional treatment of separate intravenous doses of pertuzumab and trastuzumab in Peru. To achieve this, we used EsSalud (the social security health insurance) data and assessed it through a mixed strategy, which consisted of a quantitative and a qualitative approach. The first one aimed to calculate the direct (non-drug consumables, drugs, and healthcare professionals) and indirect costs of both treatments to develop a comparison, whilst the second aimed to validate information and internalize the procedure in an EsSalud context. Overall, we found that the usage of PH FDC SC would be cost saving in EsSalud's context. Specifically, we found three main advantages. Firstly, PH FDC SC generates a savings of 62% in non-drug consumables, which helps alleviate the healthcare system budget constraint. Secondly, its adoption frees up 61 hours of treatment and observation time for a single patient per year, which in turn increases the attention capacity of the healthcare system in terms of nursing hours and chemotherapy couches. Thirdly, the reduction of clinic time supposes an advantage for the patient in the form of increased productivity and well-being. Hence, the adoption of this drug would improve the quality of life of patients while reducing costs and pressure on the healthcare system. This is aligned with the strategy of prioritizing the appropriate breast cancer treatment within the National Cancer Care Plan. In this regard, we also found that the savings produced from switching from the traditional intravenous treatment to the subcutaneous one would allow EsSalud to afford full annual costs of 2 additional treatments, but without increasing their budget. This would cover 7% of the gap of 29 patients who do not have access to full treatment. [ABSTRACT FROM AUTHOR]

Multi-taxa approaches are increasingly used because they describe complementary aspects of ecosystem dynamics from a community ecology perspective. In west-central Mexico, the complex biogeography and topography have created an environment where temperate and tropical forests converge, resulting in great biological diversity. Within this region, the Sierra de Quila Natural Protected Area (SQPA) offers an important example for understanding ecological community dynamics. We analyze the taxonomic diversity of terrestrial vertebrates in the SQPA by incorporating taxonomic levels associated with species. We evaluated the taxonomic diversity with i) an average taxonomic distinctiveness analysis (alpha diversity) and ii) an analysis of taxonomic dissimilarity and partitioning of turnover and differences in richness components (beta diversity). Tropical forests boast the highest taxonomic diversity of amphibians, reptiles, and birds, while temperate gallery forests exhibit lower values. Our results showed that terrestrial vertebrate alpha and beta diversity patterns respond mainly to contrasting vegetation types (tropical vs. temperate). Regarding beta diversity, the multi-vegetation type analysis showed the highest values for reptiles, followed by amphibians, birds, and mammals. Turnover had the highest contribution to beta diversity, while differences in richness were relevant for amphibians and reptiles, which could be related to their low mobility and sensitivity to environmental conditions. Despite the local scale, the SQPA presented high beta diversity, reflecting historical ecological processes in taxonomic composition derived from contrasting environments and constraints imposed on species. Evaluating taxonomic structure from a multi-taxa perspective is essential for conservation efforts because it allows the spatial recognition of biological assemblages as a first step for local interventions. [ABSTRACT FROM AUTHOR]

Motivation: Coexpression estimations are helpful for analysis of pathways, cofactors, regulators, targets, and human health and disease. Ideally, coexpression estimations should consider as many diverse cell types as possible and consider that available data is not uniform across tissues. Importantly, the coexpression estimations accessible today are performed on a "tissue level", which is based on cell type standardized formulations. Little or no attention is paid to overall gene expression levels. The tissue-level estimation assumes that variance expression levels are more important than mean expression levels. Here, we challenge this assumption by estimating a coexpression calculation at the "system level", which is estimated without standardization by tissue, and show that it provides valuable information. We made available a resource to view, download, and analyze both, tissue- and system-level coexpression estimations from GTEx human data. Methods: GTEx v8 expression data was globally normalized, batch-processed, and filtered. Then, PCA, clustering, and tSNE stringent procedures were applied to generate 42 distinct and curated tissue clusters. Coexpression was estimated from these 42 tissue clusters computing the correlation of 33,445 genes by sampling 70 samples per tissue cluster to avoid tissue overrepresentation. This process was repeated 20 times, extracting the minimum value provided as a robust estimation. Three metrics were calculated (Pearson, Spearman, and G-statistic) in two data processing modes, at the system-level (TPM scale) and tissue levels (z-score scale). Results: We first validate our tissue-level estimations compared with other databases. Then, by specific analyses in several examples and literature validations of predictions, we show that system-level coexpression estimation differs from tissue-level estimations and that both contain valuable information reflected in biological pathways. We also show that coexpression estimations are associated to transcriptional regulation. Finally, we present CoGTEx, a valuable resource for viewing and analyzing coexpressed genes in human adult tissues from GTEx v8 data. We introduce our web resource to list, view and explore the coexpressed genes from GTEx data. Conclusion: We conclude that system-level coexpression is a novel and interesting coexpression metric capable of generating plausible predictions and biological hypotheses; and that CoGTEx is a valuable resource to view, compare, and download system- and tissue- level coexpression estimations from GTEx data. Availability: The web resource is available at http://bioinformatics.mx/cogtex. [ABSTRACT FROM AUTHOR]

The Atlantic Forest Biome (AFB) creates an ideal environment for the proliferation of vector mosquitoes, such as Haemagogus and Sabethes species, which transmit the Yellow Fever virus (YFV) to both human and non-human primates (NHP) (particularly Alouatta sp. and Callithrix sp.). From 2016 to 2020, 748 fatal cases of YF in humans and 1,763 in NHPs were reported in this biome, following several years free from the disease. This underscores the imminent risk posed by the YFV. In this study, we examined the spatiotemporal distribution patterns of YF cases in both NHPs and humans across the entire AFB during the outbreak period, using a generalized linear mixed regression model (GLMM) at the municipal level. Our analysis examined factors associated with the spread of YFV, including environmental characteristics, climate conditions, human vaccination coverage, and the presence of two additional YFV-affected NHP species. The occurrence of epizootics has been directly associated with natural forest formations and the presence of species within the Callithrix genus. Additionally, epizootics have been shown to be directly associated with human prevalence. Furthermore, human prevalence showed an inverse correlation with urban areas, temporary croplands, and savannah and grassland areas. Further analyses using Moran's Index to incorporate the neighborhoods of municipalities with cases in each studied host revealed additional variables, such as altitude, which showed a positive correlation. Additionally, the occurrence of the disease in both hosts exhibited a spatio-temporal distribution pattern. To effectively mitigate the spread of the virus, it is necessary to proactively expand vaccination coverage, refine NHP surveillance strategies, and enhance entomological surveillance in both natural and modified environments. [ABSTRACT FROM AUTHOR]

Background: Respiratory viruses have clinical and epidemiological importance. With the COVID-19 pandemic, interest has focused on SARS-CoV-2, but as a result, the number of samples available for the differential diagnosis of other respiratory viruses has increased. Study design: Cross-sectional study. Objective: To describe the epidemiological behavior of respiratory viruses based on a laboratory-based epidemiological surveillance system using data from 2017 to 2023. Methods: Univariate, bivariate and multivariate analyses of data from a laboratory database of respiratory viruses detected by multiplex RT‒qPCR were performed. Results: A total of 4,632 samples with positive results for at least 1 respiratory virus, not including influenza or SARS-CoV-2, were analyzed. The most common virus detected was respiratory syncytial virus in 1,467 (26.3%) samples, followed by rhinovirus in 1,384 (24.8%) samples. Most of the samples were from children under 5 years of age. The age-adjusted odds ratio (OR) of death for patients infected with parainfluenza virus 4 was 4.1 (95% confidence interval [95% CI] 2.0–8.2). Conclusion: Respiratory syncytial virus and rhinovirus had the highest frequency and proportion of coinfections, whereas parainfluenza virus 4 was associated with an increased risk of death. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the generalized Langevin-Sturm-Liouville differential problems involving Caputo-Atangana-Baleanu fractional derivatives of higher orders with respect to another positive, increasing function denoted by ρ. The fixed point theorems in the framework of Kransnoselskii and Banach are utilized to discuss the existence and uniqueness of the results. In addition, the stability criteria of Ulam-Hyers, generalize Ulam-Hyers, Ulam-Hyers-Rassias, and generalize Ulam-Hyers-Rassias are investigated by non-linear analysis besides fractional calculus. Finally, illustrative examples are reinforced by tables and graphics to describe the main achievements. [ABSTRACT FROM AUTHOR]

Brain Complexity (BC) have successfully been applied to study the brain electroencephalographic signal (EEG) in health and disease. In this study, we employed recurrence entropy to quantify BC associated with the neurophysiology of movement by comparing BC in both resting state and cycling movement. We measured EEG in 24 healthy adults and placed the electrodes on occipital, parietal, temporal and frontal sites on both the right and left sides of the brain. We computed the recurrence entropy from EEG measurements during cycling and resting states. Entropy is higher in the resting state than in the cycling state for all brain regions analysed. This reduction in complexity is a result of the repetitive movements that occur during cycling. These movements lead to continuous sensorial feedback, resulting in reduced entropy and sensorimotor processing. [ABSTRACT FROM AUTHOR]

In the present study, the presence of the Enterobacterales, Staphylococcus spp., Mammaliicoccus spp., and Enterococcus spp. in cloacal samples of nestling ospreys (Pandion haliaetus), a fish-eating specialist, from Mono Lake, California, USA was examined by a multiphasic approach, including antimicrobial and biocide susceptibility testing, genotyping, and whole genome sequencing of selected isolates. The most commonly detected species was Escherichia coli, followed by Mammaliicoccus sciuri, Staphylococcus delphini, Enterococcus faecalis, Enterococcus faecium, Hafnia alvei, Klebsiella pneumoniae, Citrobacter braakii and single isolates of Edwardsiella tarda, Edwardsiella albertii, Klebsiella aerogenes, Plesiomonas shigelloides and Staphylococcus pseudintermedius. Multi-drug resistance (MDR) was observed in two E. coli isolates and in an Enterococcus faecium isolate. The MDR blaCTX-M-55-positive E. coli belonged to the pandemic clone ST58. The results of the present study suggest that nestling ospreys are exposed to MDR bacteria, possibly through the ingestion of contaminated fish. Ospreys may be good biosentinels for the presence of these microorganisms and antibiotic resistance in the local environment and the risk for other wildlife, livestock and humans. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity is one of the biggest challenges faced by modern medicine, especially when managing older patients who are also often taking multiple medications. Multimorbidity is influenced by social determinants of health, giving rise to health inequalities in the population. Here, we sought to determine the influence of social determinants of health on quality of life in patients with multimorbidity and polypharmacy. Methods and materials: This cross-sectional observational study included 573 patients aged 65–74 with multimorbidity (≥3 diseases) and polypharmacy (≥5 drugs). Corresponding data was taken drawn from the Spanish MULTIPAP study, and included social and demographic variables, and data on health-related quality of life and overall self-perceived health status, assessed using the 5-level version of the EuroQol 5-dimensional questionnaire (EQ-5D-5L). Descriptive, bivariate and multivariate analyses with logistic regression models were performed. Results: Mean patient age was 69.7 years, 55.8% of patients were female, 59.7% belonged to low social classes (V, VI), a monthly income of €1051–€1850 predominated, and the median number of diseases in the same patient was 6. Factors associated with higher quality of life were (odds ratio, OR) male gender (OR = 1.599, p = 0.013), a higher educational level (OR = 1.991, p = 0.036), an absence of urban vulnerability (OR = 1.605, p = 0.017), and the presence of medium social support (OR = 1.689, p = 0.017). Having a higher number of diseases was associated with poorer quality of life (OR = 0.912, p = 0.017). Conclusions: Our findings describe associations between social determinants of health and quality of life in patients aged 65–74 years with multimorbidity and polypharmacy. More illnesses, female gender, a lower education level, urban vulnerability, and less social support are associated with poorer quality of life, underscoring the need for a biopsychosocial approach in patient care. [ABSTRACT FROM AUTHOR]

Analysis of variability in physiological time series has been shown to be an indicator of the state of the organism. Although there is evidence of the usefulness of analysis of the amount and/or structure of variability (complexity) in cycling actions, there is limited knowledge about its application in resistance exercise. The aim of this study is to find out whether variability in acceleration signals can be an indicator of intensity level in a squat task. For this purpose, an experimental design was developed in which the following participated seventy-two participants (age = 25.7 ± 4.4 years; height = 169.2 ± 9.8 cm; body mass = 67.7 ± 11.2 kg; ratio 1RM/body mass = 1.4 ± 0.3). They performed four repetitions of back squat at loads of 10%, 30%, 50%, 70%, and 90% of 1RM. Acceleration during the exercise was recorded using an inertial measurement unit (IMU) and a force platform. The variability of the movement was then analyzed using Standard Deviation (SD), Detrended Fluctuation Analysis (DFA), Fuzzy Entropy (FuzzyEn), and Sample Entropy (SampEn). For the IMU and for the force platform, significant effects were observed in all variables (p < 0.001). In pairwise comparisons, IMU showed a significant increase in motor complexity with increasing intensity, among most intensities, in DFA, FuzzyEn and SampEn. Differences in force platform were more limited, and only DFA detected differences between most intensities. The results suggest that measures of signal and acceleration variability may be a useful indicator of the relative intensity at which a squat exercise is performed. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) has different molecular subgroups related to different risks and treatments. Tumor biopsies for BC detection are invasive and may not reflect tumor heterogeneity. Liquid biopsies have become relevant because they might overcome these limitations. We rationalize that liquid cfDNA biopsies through shallow whole genome sequencing (sWGS) could improve the detection of tumor alterations, complementing the genomic profiling. We evaluated the feasibility to detect somatic copy number alterations (SCNAs) in BC using shallow whole genome sequencing (sWGS) in cfDNA from archived samples from National Cancer Institute of Colombia patients. We sequenced tumor tissues from 38 BC patients with different molecular subtypes using a gene panel of 176 genes significantly mutated in cancer, and by liquid biopsies using sWGS on 20 paired samples to detect SCNAs and compare with the tumor samples. We identified an extensive intertumoral heterogeneity between the molecular subtypes of BC, with a mean tumor load of 602 mutations in the gene panel of tumor tissues. There was a 12.3% of concordance in deletions in the cfDNA-tumor pairs considering only the genes covered by the panel encompassing seven genes: BRCA1, CDK12, NF1, MAP2K4, NCOR1, TP53, and KEAP1 in three patients. This study shows the feasibility to complement the genomic analysis of tumor tissue biopsies to detect SCNA in BC using sWGS in cfDNA, providing a wider identification of potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Traditional pastures in temperate regions face limitations such as reduced growth and nutritional quality during the summer season. Plantain (P. lanceolata L.) offers advantages like increased yield and decreased nitrogen losses from grazing ruminants. Effective grazing management is essential for pasture health, and defoliation frequency and intensity play a pivotal role. This study aimed to evaluate plantain's regrowth, yield, and morpho-physiological and chemical responses under different defoliation frequencies and intensities, with the goal of enhancing its management in pastures. The study was conducted in pots within a controlled-environment growth chamber, examining the impact of three defoliation frequencies (based on extended leaf length: 15, 25 and 35 cm) and two defoliation intensities (5 and 8 cm of residual heights) with four replicates (24 pots as experimental units). The variables of interest were morphological characteristics, dry matter (DM) accumulation, herbage chemical composition, growth rate traits, and photosynthetic parameters. Defoliation frequency affected plantain's growth and nutritional composition. More frequent cuts (15 cm) resulted in lower DM yield per cut and lower stem content, while less frequent cuts (35 cm) produced higher values. Defoliation intensity influenced the proportion of leaves and stems in the total DM, with 5 cm cuts favoring leaves. Nutrient content was also affected by defoliation frequency, with less frequent cuts (35 cm) showing lower crude protein concentration and metabolizable energy content but higher neutral detergent fiber and water-soluble carbohydrate concentration. Plantain's growth rate variables were mainly influenced by defoliation frequency, with less frequent cuts promoting faster leaf appearance and growth of new leaves. The basal fluorescence variables and chlorophyll content were affected by cutting frequency, being highest when cut less frequently (35 cm), while no differences were found in the actual quantum efficiency among different defoliation frequencies and intensities. The fraction of light dedicated to non-photochemical quenching was highest when cut less frequently and more intensively. Overall, defoliation at 25 cm of extended leaf length balanced plantain forage quality and regrowth capacity. [ABSTRACT FROM AUTHOR]

AimsTo evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral antihyperglycaemic drugs.MethodsA post hoc patient-level meta-analysis was performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3 (insulin-naïve [N = 878]), multicentre, randomised, open-label, parallel-group, phase 3a trials of similar design. Endpoints analysed included HbA1c, hypoglycaemia and adverse events, investigated in subgroups of participants with and without concomitant DPPIVi use.ResultsOf 1689 participants randomised, 107 (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares mean change in HbA1c (baseline to month 6) was comparable between treatment groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment effect across subgroups, p = 0.753), although group sizes were unbalanced. The cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, and the risk and annualised rate of such events, were consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and 05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla-100 groups, respectively, and was not affected by DPPIVi use. The adverse event profile was similar between treatment groups and DPPIVi subgroups.ConclusionsGlycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia during the night and at any time of day (24 h), irrespective of concomitant DPPIVi use.Trial registrationClinicalTrials.gov NCT01499095; NCT01676220.

Poison frogs acquire chemical defenses from the environment for protection against potential predators. These defensive chemicals are lipophilic alkaloids that are sequestered by poison frogs from dietary arthropods and stored in skin glands. Despite decades of research focusing on identifying poison frog alkaloids, we know relatively little about how environmental variation and subsequent arthropod availability impacts alkaloid loads in poison frogs. We investigated how seasonal environmental variation influences poison frog chemical profiles through changes in the diet of the Climbing Mantella (Mantella laevigata). We collected M. laevigata females on the Nosy Mangabe island reserve in Madagascar during the wet and dry seasons and tested the hypothesis that seasonal differences in rainfall is associated with changes in diet composition and skin alkaloid profiles of M. laevigata. The arthropod diet of each frog was characterized into five groups (i.e. ants, termites, mites, insect larvae, or other) using visual identification and cytochrome oxidase 1 DNA barcoding. We found that frog diet differed between the wet and dry seasons, where frogs had a more diverse diet in the wet season and consumed a higher percentage of ants in the dry season. To determine if seasonality was associated with variation in frog defensive chemical composition, we used gas chromatography / mass spectrometry to quantify alkaloids from individual skin samples. Although the assortment of identified alkaloids was similar across seasons, we detected significant differences in the abundance of certain alkaloids, which we hypothesize reflects seasonal variation in the diet of M. laevigata. We suggest that these variations could originate from seasonal changes in either arthropod leaf litter composition or changes in frog behavioral patterns. Although additional studies are needed to understand the consequences of long-term environmental shifts, this work suggests that alkaloid profiles are relatively robust against short-term environmental perturbations.