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Abstract Background Long non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources). Methods INFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell proliferation and chemotherapeutic drug response. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiation. Finally, we established a mouse K562 leukemia xenograft model to determine whether SNHG6 KD attenuates tumor growth in vivo. Results The INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regulated by hematopoiesis-associated transcription factors. SNHG6 KD reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenuated tumor growth in vivo. Conclusions Our approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with roles in hematopoiesis and leukemia. Such approaches can be readily applied to identify novel targets for precision medicine.

Designing an exoskeleton that can improve user capabilities is a challenging task, and most designs rely on experiments to achieve this goal. A different approach is to use simulation-based designs to determine optimal device parameters. Most of these simulations use full trajectory tracking limb kinematics during a natural gait as a reference. However, exoskeletons typically change the natural gait kinematics of the user. Other types of simulations assume that human gait is optimized for a cost function that combines several objectives, such as the cost of transport, injury prevention, and stabilization. In this study, we use a 2D OpenSim model consisting of 10 degrees of freedom and considering 18 muscles, together with the Moco optimization tool, to investigate the differences between these two approaches with respect to running with a passive knee exoskeleton. Utilizing this model, we test the effect of a full trajectory tracking objective with different weights (representing the importance of the objective in the optimization cost function) and show that when using weights that are typically used in the literature, there is no deviation from the experimental data. Next, we develop a multi-objective cost function with foot clearance term based on peak knee angle during swing, that achieves trajectories similar (RMSE=7.4 deg) to experimental running data. Finally, we investigate the effect of different parameters in the design of a clutch-based passive knee exoskeleton (1.5 kg at each leg) and find that a design that utilizes a 2.5 Nm/deg spring achieves an improvement of up to 8% in net metabolic energy. Our results show that tracking objectives in the cost function, even with a low weight, hinders the simulation’s ability to change the gait trajectory. Thus, there is a need for other predictive simulation methods for exoskeletons.

El presente artículo tiene como objetivo analizar la crisis financiera de 2008 a partir del otorgamiento del Premio Nobel de Economía en 2022, concedido a los economistas Douglas W. Diamond, Philip H. Dybvig y Ben S. Bernanke. Se resalta la importancia del papel de la banca durante un periodo de recesión. La idea es comprender y abordar dicha crisis, a partir de los hallazgos de los galardonados, quienes demostraron lo crucial que es detener las quiebras bancarias generalizadas. Este análisis subraya que las lecciones extraídas de la crisis de las hipotecas subprime son fundamentales para garantizar la estabilidad económica global así como para orientar las regulaciones en un mundo cada vez más interconectado. Debido a que la crisis subprime y la quiebra de Lehman Brothers marcaron el colapso, que da como resulta una crisis bancaria global, el artículo inicia con un enfoque de dicha crisis, con el fin de exploran los antecedentes y causas que llevan a la creación de la burbuja inmobiliaria. Para contrarrestar el colapso y la quiebra bancaria global se implementaron regulaciones como la Ley Dodd-Frank y Basilea III, junto con un aumento del gasto gubernamental y tasas de interés cercanas a cero. La negligencia regulatoria y los riesgos no considerados por los bancos fueron factores fundamentales. Por último, se examina de forma breve la respuesta de la política monetaria a la recesión provocada por la pandemia durante 2020. A continuación como la Reserva Federal y otros bancos centrales recurrieron nuevamente a tasas de interés cercanas a cero y la relajación cuantitativa para impulsar la economía.

Abstract In this study, we examined a mathematical model of breast cancer (BC) treatment that combines an oral oestrogen receptor inhibitor, AZD9496 with Palbociclib, a selective inhibitor of cyclin- dependent kinases CDK4 and CDK6. Treatment is described by analytical functions that enable us to control the dosage and time interval of the treatment, thus personalising the treatment for each patient. Initially, we investigated the effect of each treatment separately, and finally, we investigated the combination of both treatments. By applying numerical simulations, we confirmed that the combination of AZD9496 with palbociclib was the optimal treatment for BC. The dosage of AZD9496 increased and decreased throughout the treatment period, while the intervals were constant between treatments. Palbociclib changed almost cyclically, whereas the time intervals remained constant. To investigate the mathematical model, we applied the singularly perturbed homotopy analysis method, which is a numerical algorithm. The significant advantage of this method is that the mathematical model does not have to contain a small parameter (as is standard in perturbation theory). However, it is possible to artificially introduce a small parameter into the system of equations, making it possible to study the model using asymptotic methods.

Riboflavin, an essential vitamin for humans, is extensively used in various industries, with its global demand being met through fermentative processes. Hyphopichia wangnamkhiaoensis is a novel dimorphic yeast species capable of producing riboflavin. However, the nutritional factors affecting riboflavin production in this yeast species remain unknown. Therefore, we conducted a kinetic study on the effects of various nutritional factors—carbon and energy sources, nitrogen sources, vitamins, and amino acids—on batch riboflavin production by H. wangnamkhiaoensis. Batch experiments were performed in a bubble column bioreactor to evaluate cell growth, substrate consumption, and riboflavin production. The highest riboflavin production was obtained when the yeast growth medium was supplemented with glucose, ammonium sulfate, biotin, and glycine. Using these chemical components, along with the mineral salts from Castañeda-Agullo’s culture medium, we formulated a novel, low-cost, and effective culture medium (the RGE medium) for riboflavin production by H. wangnamkhiaoensis. This medium resulted in the highest levels of riboflavin production and volumetric productivity, reaching 16.68 mg/L and 0.713 mg/L·h, respectively, within 21 h of incubation. These findings suggest that H. wangnamkhiaoensis, with its shorter incubation time, could improve the efficiency and cost-effectiveness of industrial riboflavin production, paving the way for more sustainable production methods.

Given the health benefits of carotenoids, it is crucial to evaluate their levels in patients undergoing malabsorptive procedures like one anastomosis gastric bypass (OAGB). This study aimed to assess serum carotenoid levels before and 6 months following OAGB. Prospectively collected data from patients who underwent primary OAGB were analyzed. Data included anthropometrics, dietary intake assessments, and biochemical tests. Serum samples were analyzed for lipid profile and serum carotenoids, including lutein, zeaxanthin, α-carotene, β-carotene, phytofluene, ζ-carotene, and lycopene. Data from 27 patients (median age 47.0 years and 55.6% female) were available before and 6 months post-OAGB. The median pre-surgical BMI was 39.5 kg/m2, and the median excess weight loss at 6 months post-surgery was 63.9%. Significant decreases in all carotenoid levels were observed over time (p < 0.001 for all). A median relative decline of 65.1% in absolute total carotenoid levels and 12.7% in total cholesterol levels were found. No associations were observed between changes in clinical outcomes and carotenoid levels during the study period. This study reveals significant decreases in carotenoid levels within the first 6 months following OAGB. Nutritional intervention studies are needed to explore how incorporating carotenoid-rich foods affects post-surgery carotenoid levels and clinical outcomes.

Objectives To compare the discussions from two panels on the concept of palliative care quality for patients with advanced cancer, exploring the priorities reflected in each group’s perspectives.Design We convened two RAND-UCLA appropriateness panel discussions on palliative care quality in advanced cancer. Discussions were audio-recorded and transcribed verbatim. Panel transcripts were analysed thematically using a matrix approach to examine perceptions and experiences of quality.Setting Discussions were framed within the context of advanced cancer care and palliative care.Participants The patient–caregiver panel had 9 patients with current or a history of cancer and caregivers, and the practitioner panel had 10 expert practitioners representing fields of oncology, primary care, social work, palliative care, nursing, pain management and ethics.Results Our analysis identified three thematic categories for understanding quality common across both groups and nine subthemes within those categories. At the highest level, quality was conceived as: (1) the patient and caregiver experience of care, (2) technical competence and (3) the structure of health system. Among the subthemes, four were present in only one of the two group’s discussions: ‘purpose and action’ was specific to the patient–caregiver panel, whereas ‘adhering to best medical practice’, ‘mitigating unintended consequences and side effects’, and ‘health system resources and costs’ were specific to the practitioner panel.Conclusions While both panels aligned on the three key domains of quality, the particular dimensions through which they perceived quality varied in relation to their experience and role as a professional provider of care versus recipient of healthcare services. These differences suggest the importance of adopting a collaborative approach to quality measurement and improvement so that the values of all interested parties are represented in improvement efforts.

The structure-activity relationships data available in public databases of inhibitors of DNA methyltransferases (DNMTs), families of epigenetic targets, plus the structural information of DNMT1, enables the development of a robust structure-based drug design strategy to study, at the molecular level, the activity of DNMTs inhibitors. In this study, we discuss a consensus molecular docking strategy to aid in explaining the activity of small molecules tested as inhibitors of DNMT1. The consensus docking approach, which was based on three validated docking algorithms of different designs, had an overall good agreement with the experimental enzymatic inhibition assays reported in the literature. The docking protocol was used to explain, at the molecular level, the activity profile of a novel DNMT1 inhibitor with a distinct chemical scaffold whose identification was inspired by de novo design and complemented with similarity searching.

Objetivo: Describir las características del uso de una app preventiva en la población peruana durante su primer año de operaciones, en el periodo comprendido entre el 2019 y 2020. Materiales y métodos: Estudio de tipo descriptivo, transversal y retrospectivo, donde se revisó la base de datos de la app preventiva Salud Total respecto a las características demográficas y forma de uso en la población peruana durante su primer año de operaciones. Se analizaron las variables sociodemográficas (sexo y edad) y las formas de uso (los datos de salud ingresados, los hallazgos patológicos encontrados, la recurrencia de uso y el tipo y la cantidad de servicios solicitados). El análisis y procesamiento de los datos descriptivos se realizaron con el programa Microsoft Excel. Resultados: El número de usuarios que descargaron y se registraron en la app fue 9737 personas. Con respecto al sexo, la proporción fue similar, y el grupo etario predominante fue entre 21 y 50 años. Se obtuvieron 2304 datos de salud que los usuarios registraron voluntariamente, de los cuales los más reportados fueron el peso y la talla (45,3 %), seguidos de la presión arterial (20,4 %), la hemoglobina (17,1 %) y la circunferencia abdominal. Se encontraron hallazgos patológicos en los datos registrados tales como la presión arterial elevada (25,7 %) y el peso elevado (58,5 %), entre otros. Asimismo, los usuarios solicitaron por medio de la app un total de 1072 servicios de salud de diversos tipos, entre los cuales destacan la atención médica (58 %) y el laboratorio clínico (32 %). Conclusiones: Los usuarios pudieron registrarse e interactuar con una app preventiva con el fin de controlar su bienestar, y la usaron tanto para añadir sus datos de salud como para solicitar servicios médicos de forma remota, lo que puede significar una nueva herramienta de intervención para direccionar acciones preventivas, la atención oportuna de enfermedades y una nueva fuente de datos para la investigación en salud.

Abstract Background We aimed to assess the correlation between ovarian hyperstimulation syndrome (OHSS) in the early course of in vitro fertilization (IVF) pregnancies and obstetric outcomes. Methods We identified records of patients admitted due to OHSS following IVF treatment at our institution between 2008 and 2020. Cases were included if pregnancy resulted in a live singleton delivery (OHSS group). OHSS cases were matched at a 1:5:5 ratio with live singleton deliveries following IVF with fresh embryo transfer (fresh transfer group) and frozen embryo transfer (FET group), according to maternal age and parity. Computerized files were reviewed, and maternal, obstetric and neonatal outcomes compared. Results Overall, 44 OHSS cases were matched with 220 fresh transfer and 220 FET pregnancies. Patient demographics were similar between the groups, including body mass index, smoking and comorbidities. Gestational age at delivery, the rate of preterm births, preeclampsia and cesarean delivery were similar between the groups. Placental abruption occurred in 6.8% of OHSS pregnancies, 1.4% of fresh transfer pregnancies and 0.9% of FET pregnancies (p=0.02). On post-hoc analysis, the rate of placental abruption was significantly higher in OHSS pregnancies, compared with the two other groups, and this maintained significance after adjustment for confounders. Birthweights were 3017 ± 483, 3057 ± 545 and 3213 ± 542 grams in the OHSS, fresh transfer and FET groups, respectively (p=0.004), although the rate of small for gestational age neonates was similar between the groups. Conclusions OHSS in the early course of IVF pregnancies is associated with an increased risk of placental abruption.

Este documento proporciona una visión general de la construcción de un molino de martillos de tamaño compacto de bajo costo para uso en laboratorio. Reducir el tamaño de partícula de diversos materiales para estudiar sus propiedades fisicoquímicas mediante la construcción de un molino de martillos. El molino de martillos fue construido con materiales que se pueden obtener en almacenes de equipos industriales y residuos vehiculares. La metodología de construcción se basó en la mecánica de precisión y la metalurgia. Desarrollos Tecnológicos Teck S. A. y el Laboratorio de Biomasa de la Facultad de Química de la Universidad de Costa Rica, San José, Costa Rica, en 2020. Los materiales lignocelulósicos residuales se molieron del racimo vacío de palma aceitera de fruta (Elaeis guineensis), la cáscara de nuez de la palma de fruta Coyol (Acrocomia spp.), rocas, cáscara de coco, madera, lodo y escoria de aluminio. La construcción del molino de martillos es de forma compacta y versátil porque permite moler una amplia variedad de materiales para procesos de investigación que requieren la reducción de materiales orgánicos e inorgánicos. Debido a su modesto tamaño, se puede colocar en un laboratorio y dado que su fuente de alimentación es de 110 voltios, no son necesarios requisitos especiales.

Background: One-anastomosis gastric bypass (OAGB) is an emerging metabolic bariatric surgery (MBS) type used in both primary OAGB (pOAGB) and revisional OAGB (rOAGB). We studied ≤30-day outcomes of pOAGB and rOAGB and identified predictors of early complications. Methods: Electronic medical records of all OAGBs performed between January 2017 and December 2021 at a high-volume bariatric clinic in Israel comprising four hospital centers were scanned retrospectively using specialized data software (MDClone software, version 6.1). Data gathered were patients’ characteristics, surgical procedure, and ≤30-day complications with Clavien–Dindo Classification (CDC). Multivariate logistic regression analyses were used to identify factors related to early complications of pOAGB and rOAGB. Results: A total of 6722 patients underwent a pOAGB (n = 5088, 75.7%) or rOAGB (n = 1634, 24.3%) procedure at our institution. Preoperative mean age and body mass index (BMI) were 40.6 ± 11.5 years and 41.2 ± 4.6 kg/m2, respectively. Early complications occurred in 258 (3.8%) patients (176 pOAGB and 82 rOAGB) and included mainly bleeding (n = 133, 2.0%), leaks (n = 31, 0.5%), and obstruction/strictures (n = 19, 0.3%). CDC complications for grades 1–2 and grades 3a-–5 were 1.5% and 1.6%, respectively. The overall mortality rate was 0.03% (n = 2). Age, operative time ≥3 h, and any additional concomitant procedure were independent predictors of early complications following pOAGB, while a diagnosis of diabetes mellitus and operative time ≥3 h were independent predictors of early complications following rOAGB. Conclusions: OAGB was found to be a safe primary and revisional MBS procedure in the ≤30-postoperative day term. The most common complications were gastrointestinal bleeding, leaks, and obstruction/stricture.

Inspired by the ongoing disruption to businesses across the world, this research focuses on how the COVID-19 pandemic has affected the contribution of eCommerce to small and medium-sized enterprises (SMEs). Our study seeks to establish an eCommerce-driven response to this natural disruption, by asking the questions; How do eCommerce platforms impact SMEs? How does eCommerce affect an SME’s three major business functions during a global disruption? We employ a qualitative case study method, using interviews as our primary data source, along with secondary data from industry and company records. We discuss these case studies through the framework of the actor network theory (ANT), identifying eCommerce and other platforms that SMEs use as actors in their network. We interviewed eight SMEs involved in the physical sale and distribution of consumer goods, each of which had been operating for at least two years and had a maximum of 70 employees. On average, we found that 44% of the SMEs in this study benefitted from using eCommerce in key business areas, with 46% improving their operations, 47% improving sales and marketing, and 39% improving finance. We also found that SME adoption of eCommerce during the pandemic grew in response to these benefits. Of the eight companies we studied, four had begun developing full eCommerce operations and three more planned to develop them as the global situation further normalizes.

Quality measurement is typically the domain of clinical experts and health system leaders; patient/caregiver perspectives are rarely solicited. We aimed to describe and integrate clinician and patient/caregiver conceptualizations of high-quality palliative symptom care for patients receiving care for advanced cancer within the US Veterans Health Administration in the context of existing quality measures. We conducted a secondary qualitative analysis of transcripts from prioritization discussions of process quality measures relevant to cancer palliative care. These discussions occurred during 2 modified RAND-UCLA appropriateness panels: a panel of 10 palliative care clinical expert stakeholders (7 physicians, 2 nurses, 1 social worker) and a panel of 9 patients/caregivers with cancer experience. Discussions were recorded, transcribed, and independently double-coded using an a priori logical framework. Content analysis was used to identify subthemes within codes and axial coding was used to identify crosscutting themes. Patients/caregivers and clinical experts contributed important perspectives to 3 crosscutting themes. First, proactive elicitation of symptoms is critical. Patients/caregivers especially emphasized importance of comprehensive and proactive screening and assessment, especially for pain and mental health. Second, screening and assessment alone is not enough; information elicited from patients must inform care. Measuring screening/assessment and management care processes separately has important limitations. Lastly, high-quality symptom management can be broadly defined if it is patient-centered; high-quality care takes an individualized approach and might include non-medical or non-pharmacological symptom management. Integrating the perspectives of clinical experts and patients/caregivers is critical for health systems to consider as they design and implement quality measures for palliative cancer care.

This article analyses the accountability of intelligence agencies in Spain and Brazil. Drawing from critical intelligence studies, this article will argue that the goal of accountability is to expand legitimacy by incorporating the civil society. This requires redeveloping the scope of intelligence and its audience beyond legal norms and traditional decision-makers. To do so, the article will consider the following actors: 1) the media; 2) whistleblowers and leaks; 3) scholars; and 4) fiction writers. These actors may complement intelligence by gathering information or acting as knowledge advisory groups. Moreover, they can also challenge intelligence by promoting deeper scrutiny and transparency, while constructing archetypes that represent secret agencies. The conclusion will summarize the strengths and limitations deriving from these actors to promote accountability. It will also claim that, through a critical approach, exploring new accountability forms are necessary to expand the social legitimacy of intelligence policies. Received: 2022-10-07 Revised: 2022-01-05

Circadian and circannual cycles trigger physiological changes whose reflection on human transcriptomes remains largely uncharted. We used the time and season of death of 932 individuals from GTEx to jointly investigate transcriptomic changes associated with those cycles across multiple tissues. Overall, most variation across tissues during day-night and among seasons was unique to each cycle. Although all tissues remodeled their transcriptomes, brain and gonadal tissues exhibited the highest seasonality, whereas those in the thoracic cavity showed stronger day-night regulation. Core clock genes displayed marked day-night differences across multiple tissues, which were largely conserved in baboon and mouse, but adapted to their nocturnal or diurnal habits. Seasonal variation of expression affected multiple pathways, and it was enriched among genes associated with the immune response, consistent with the seasonality of viral infections. Furthermore, they unveiled cytoarchitectural changes in brain regions. Altogether, our results provide the first combined atlas of how transcriptomes from human tissues adapt to major cycling environmental conditions. This atlas may have multiple applications; for example, drug targets with day-night or seasonal variation in gene expression may benefit from temporally adjusted doses.

Emotion recognition is key to interpersonal communication and to human-machine interaction. Body expression may contribute to emotion recognition, but most past studies focused on a few motions, limiting accurate recognition. Moreover, emotions in most previous research were acted out, resulting in non-natural motion, which is unapplicable in reality. We present an approach for emotion recognition based on body motion in naturalistic settings, examining authentic emotions, natural movement, and a broad collection of motion parameters. A lab experiment using 24 participants manipulated participants' emotions using pretested movies into five conditions: happiness, relaxation, fear, sadness, and emotionally-neutral. Emotion was manipulated within subjects, with fillers in between and a counterbalanced order. A motion capture system measured posture and motion during standing and walking; a force plate measured center of pressure location. Traditional statistics revealed nonsignificant effects of emotions on most motion parameters; only 7 of 229 parameters demonstrate significant effects. Most significant effects are in parameters representing postural control during standing, which is consistent with past studies. Yet, the few significant effects suggest that it is impossible to recognize emotions based on a single motion parameter. We therefore developed machine learning models to classify emotions using a collection of parameters, and examined six models: k-nearest neighbors, decision tree, logistic regression, and the support vector machine with radial base function and linear and polynomial functions. The decision tree using 25 parameters provided the highest average accuracy (45.8%), more than twice the random guess for five conditions, which advances past studies demonstrating comparable accuracies, due to our naturalistic setting. This research suggests that machine learning models are valuable for emotion recognition in reality and lays the foundation for further progress in emotion recognition models, informing the development of recognition devices (e.g., depth camera), to be used in home-setting human-machine interactions.

Research and the commercial use of exoskeletons that augment human activities are rapidly growing. However, the progress of the two is hindered by the time-consuming and costly process of designing and evaluating the exoskeleton. One of the solutions to reduce both is the use of simulations that model the users, exoskeleton, and their interaction. At the same time, most simulations focus on continuous tasks, such as walking, running, and industrial activities. The augmentation of human capability is essential in fast motion tasks (i.e., jumping, throwing), where the muscles are producing their maximum force. Thus, this study implemented a simulation of passive exoskeleton–human interactions using OpenSim and Moco software for optimal control to find muscle excitation that maximizes vertical jump height. The models include a planar human model with ankle, knee, and hip joints. The muscles were modeled as torque actuators for each joint, with a flexor and an extensor, and passive torques representing each joint’s ligaments. The simulation was used to study: a) the effect of different spring stiffness at the knee, hip, and ankle joints and combinations of these joints; b) multi-joints vs. single joints; c) the effect of an elliptic pulley and different initial engagement angle for springs. The results revealed that the jump height increased as the spring became stiffer, up to a maximum point. For a single joint, the knee exoskeleton was the most effective, compared with the hip and ankle joint exoskeletons. The multi-joint exoskeleton was slightly better than the single knee joint. If maximum spring tension is a limiting factor, an elliptic pulley has an advantage relative to a round pulley. An initial angle of engagement (with equal work) other than zero up to approximately 50 degrees does not decrease the jump height.

Most exoskeletons are designed to reduce the metabolic costs of performing aerobic tasks such as walking, running, and hopping. This study presents an exoskeleton that boosts vertical jumping—a fast, short movement during which the muscles are exerted at peak capacity. It was hypothesized that a passive exoskeleton would increase vertical jump height without requiring external energy input. The device comprises springs that work in parallel with the muscles of the quadriceps femoris. The springs store mechanical energy during knee flexion (the negative work phase) and release that energy during the subsequent knee extension (the positive work phase), augmenting the muscles. Ten healthy participants were evaluated in two experimental sessions. In the first session, the participants jumped without receiving instructions on how to use the exoskeleton, and the results showed no difference in jump height when jumping with the exoskeleton or jumping without it. In the second session, the participants were instructed to achieve deeper initial squat heights at the start of the jump. This resulted in a 6.4% increase in average jump height compared to jumping without the exoskeleton (each participant performed five jumps for each the two conditions). This is the first time that a passive exoskeleton has been shown to improve the height of a vertical jump from a dead stop.

This multi-center study evaluated a novel microscope system capable of quantitative phase microscopy (QPM) for label-free sperm-cell selection for intracytoplasmic sperm injection (ICSI). Seventy-three patients were enrolled in four in vitro fertilization (IVF) units, where senior embryologists were asked to select 11 apparently normal and 11 overtly abnormal sperm cells, in accordance with current clinical practice, using a micromanipulator and 60× bright field microscopy. Following sperm selection and imaging via QPM, the individual sperm cell was chemically stained per World Health Organization (WHO) 2021 protocols and imaged via bright field microscopy for subsequent manual measurements by embryologists who were blinded to the QPM measurements. A comparison of the two modalities resulted in mean differences of 0.18 µm (CI −0.442–0.808 µm, 95%, STD—0.32 µm) for head length, −0.26 µm (CI −0.86–0.33 µm, 95%, STD—0.29 µm) for head width, 0.17 (CI −0.12–0.478, 95%, STD—0.15) for length–width ratio and 5.7 for acrosome–head area ratio (CI −12.81–24.33, 95%, STD—9.6). The repeatability of the measurements was significantly higher in the QPM modality. Surprisingly, only 19% of the subjectively pre-selected normal cells were found to be normal according to the WHO2021 criteria. The measurements of cells imaged stain-free through QPM were found to be in good agreement with the measurements performed on the reference method of stained cells imaged through bright field microscopy. QPM is non-toxic and non-invasive and can improve the clinical effectiveness of ICSI by choosing sperm cells that meet the strict criteria of the WHO2021.

The yeast Hyphopichia wangnamkhiaoensis excretes a brilliant yellow fluorescent compound into its growth culture. In this study, we isolated and identified this compound using reverse-phase high-performance liquid chromatography-diode array detector (RP-HPLC-DAD) as well as 1H NMR and UV–Vis spectroscopy. Two of the three RP-HPLC-DAD methods used successfully separated the fluorescent compound and involved (1) a double separation step with isocratic flow elution, first on a C18 column and later on a cyano column, and (2) a separation with a linear gradient elution on a phenyl column. The wavelengths of maximum absorption of the fluorescent compound-containing HPLC fractions (~224, 268, 372, and 446 nm) are in good agreement with those exhibited by flavins. The 1H NMR spectra revealed methyl (δ 2.30 and 2.40) and aromatic proton (δ 7.79 and 7.77) signals of riboflavin. The 1H NMR spectra of the samples spiked with riboflavin confirmed that the brilliant yellow fluorescent compound is riboflavin. The maximum excitation and emission wavelengths of the fluorescent compound were 448 and 528 nm, respectively, which are identical to those of riboflavin.

The increase in people’s longevity has, consequently, led to more brain involvement and neurodegenerative diseases, which can become complicated and lead to chronic degenerative diseases, thereby presenting greater public health problems. Medicinal plants have been used since ancient times and contain high concentrations of molecules, including polyphenols. It has been proven that polyphenols, which are present in various natural sources can provide curative effects against various diseases and brain disorders through neuroprotective effects. These neuroprotective effects are mainly attributed to their ability to cross the blood–brain barrier, eliminate reactive oxygen species, and cause the chelation of metal ions. Polyphenols increase the concentration of neurotrophic factors and bind directly to the membrane receptors of these neurotrophic factors, to modulate and activate the signaling cascades that allow the plasticity, survival, proliferation, and growth of neuronal cells, thereby allowing for better learning, memory, and cognition. Moreover, polyphenols have no serious adverse side effects resulting from their consumption.

PURPOSESeven major palliative care (PC) centers in India were mentored through the Palliative Care—Promoting Assessment and Improvement of the Cancer Experience (PC-PAICE) by US and Australian academic institutions to implement a quality improvement (QI) project to improve the accessibility and quality of PC at their respective centers. The objective was to evaluate the experiences of teams in implementing QI methods across diverse geographical settings in India.METHODSA quota sampling approach was used to elicit perspectives of local stakeholders at each site. The Consolidated Framework for Implementation Research informed development of a semistructured interview guide. Analysis leveraged deductive and inductive approaches.RESULTSWe interviewed 44 participants (eight organizational leaders, 12 clinical leaders, and 24 team members) at seven sites and identified five themes. (1) Implementing QI methods enabled QI teams to think analytically to solve a complex problem and to identify resources. (2) Developing a problem statement by identifying specific gaps in patient care fostered team collaboration toward a common goal. (3) Making use of QI tools (eg, A3 process) systematically provided a new, straightforward QI toolkit and improved QI teams' conceptual understanding. (4) Enhancing stakeholder engagement allowed shared understanding of QI team members' roles and processes and shaped interventions tailored to the local context. (5) Designing less subjective processes for patient care such as assessment scales to identify patient's symptomatic needs positively changed work practices and culture.CONCLUSIONEngaging and empowering multiple stakeholders to use QI methods facilitated the expansion and improvement of PC and cancer services in India. PC-PAICE demonstrated an efficient, effective way to apply QI methods in an international context. The impact of PC-PAICE is being magnified by developing a cadre of Indian QI leaders.

Biomechanical energy harvesters are designed to generate electrical energy from human locomotion (e.g., walking) with minimal or no additional effort by the users. These harvesters aim to carry out the work of the muscles during phases in locomotion where the muscles are acting as brakes. Currently, many harvesters focus on the knee joint during late swing, which is only one of three phases available during the gait cycle. For the device to be successful, there is a need to consider design components such as the motor/generator and the gear ratio. These components influence the amount of electrical energy that could be harvested, metabolic power during harvesting, and more. These various components make it challenging to achieve the optimal design. This paper presents a design of a knee harvester with a direct drive that enables harvesting both in flexion and extension using optimization. Subsequently, two knee devices were built and tested using five different harvesting levels. Results show that the 30% level was the best, harvesting approximately 5 W of electricity and redacting 8 W of metabolic energy compared to walking with the device as a dead weight. Evaluation of the models used in the optimization showed a good match to the system model but less for the metabolic power model. These results could pave the way for an energy harvester that could utilize more of the negative joint power during the gait cycle while reducing metabolic effort.

Mechanisms that control ‘beige/brite’ thermogenic adipose tissue development may be harnessed to improve human metabolic health. To define these mechanisms, we developed a species-hybrid model in which human mesenchymal progenitor cells were used to develop white or thermogenic/beige adipose tissue in mice. The hybrid adipose tissue developed distinctive features of human adipose tissue, such as larger adipocyte size, despite its neurovascular architecture being entirely of murine origin. Thermogenic adipose tissue recruited a denser, qualitatively distinct vascular network, differing in genes mapping to circadian rhythm pathways, and denser sympathetic innervation. The enhanced thermogenic neurovascular network was associated with human adipocyte expression of THBS4, TNC, NTRK3, and SPARCL1, which enhance neurogenesis, and decreased expression of MAOA and ACHE, which control neurotransmitter tone. Systemic inhibition of MAOA, which is present in human but absent in mouse adipocytes, induced browning of human but not mouse adipose tissue, revealing the physiological relevance of this pathway. Our results reveal species-specific cell type dependencies controlling the development of thermogenic adipose tissue and point to human adipocyte MAOA as a potential target for metabolic disease therapy.

El mercado ofrece turbinas eólicas de pequeña escala como una solución parcial para reducir la factura eléctrica en viviendas. Sin embargo, en algunos casos el rendimiento ofrecido supera el obtenido, esto se debe a las bajas velocidades del viento en las zonas residenciales y al efecto de la turbulencia sobre los aerogeneradores. El objetivo de este trabajo es determinar la influencia local de los obstáculos en la turbulencia y describir el desarrollo de la turbulencia en función de la altura, comparando dos torres meteorológicas: una colocada entre árboles y otra colocada en una zona sin obstáculos cercanos. Se pretende determinar si dentro de un paisaje específico pueden encontrarse lugares con menor turbulencia debido a una reducción de los obstáculos de manera local. Las mediciones obtenidas entre octubre de 2018 y septiembre de 2019 se procesan y mediante histogramas se compara la intensidad de turbulencia en función de la altura. Se encuentra que la turbulencia es menor conforme aumenta la altura en la torre que está inmersa entre árboles; con valores de 30% a 14 metros de altura y de 50% a 6 m de altura. En el caso de la torre que está sin obstáculos, en su entorno cercano, la turbulencia es menos dependiente de la altura, con valores de 30% a 12 metros de altura y de 40% a 4 m de altura. Se reporta un valor de intensidad de turbulencia cercano al 30% como el más frecuente entre los datos obtenidos por los diez anemómetros del estudio.

Low-cost 3D video sensors equipped with routines for extracting skeleton data facilitate the widespread use of virtual reality (VR) for rehabilitation. However, the accuracy of the extracted skeleton data is often limited. Accuracy can be improved using a motion tracker, e.g., using a recurrent neural network (RNN). Yet, training an RNN requires a considerable amount of relevant and accurate training data. Training databases can be obtained using gold-standard motion tracking sensors. This limits the use of the RNN trackers in environments and tasks that lack accessibility to gold-standard sensors. Digital goniometers are typically cheaper, more portable, and simpler to use than gold-standard motion tracking sensors. The current work suggests a method for generating accurate skeleton data suitable for training an RNN motion tracker based on the offline fusion of a Kinect 3D video sensor and an electronic goniometer. The fusion applies nonlinear constraint optimization, where the constraints are based on an advanced shoulder-centered kinematic model of the arm. The model builds on the representation of the arm as a triangle (the arm triangle). The shoulder-centered representation of the arm triangle motion simplifies constraint representation and consequently the optimization problem. To test the performance of the offline fusion and the RNN trained using the optimized data, arm motion of eight participants was recorded using a Kinect sensor, an electronic goniometer, and, for comparison, a passive-marker-based motion tracker. The data generated by fusing the Kinect and goniometer recordings were used for training two long short-term memory (LSTM) RNNs. The input to one RNN included both the Kinect and the goniometer data, and the input to the second RNN included only Kinect data. The performance of the networks was compared to the performance of a tracker based on a Kalman filter and to the raw Kinect measurements. The accuracy of the fused data was high, and it considerably improved data accuracy. The accuracy for both trackers was high, and both were more accurate than the Kalman filter tracker and the raw Kinect measurements. The developed methods are suitable for integration with immersive VR rehabilitation systems in the clinic and the home environments.

The main key drivers of vulnerability for marine species are anthropogenic stressors, ranging from pollution and fishing to climate change. The widely documented impacts of fishing activities on marine species, the growing concern about the population status of many marine species, and the increase in per capita consumption of marine products worldwide have led to the development of environmentally responsible fishing standards and initiatives to inform consumers about the health status of the species. In Mexico, fishing is a vital source of jobs and food security for many coastal communities, but the population status of many species of commercial importance has not been evaluated. Management efforts and fisheries certification procedures and standards to achieve the sustainability of many Mexican fisheries are hindered by a lack of biological and fishery data for many species. In this study, a risk assessment methodology for data-limited fisheries, a Productivity, and Susceptibility Analysis was used to estimate the relative vulnerability of marine invertebrates and fishes commercially important in Mexico to fishing. Ninety-eight invertebrates, 66 elasmobranchs, and 367 bony fish were analyzed. The vulnerability among the 531 evaluated species is high for 115 (22%), moderate for 113 (21%), and low for 303 (57%). The most vulnerable species are the Mexican geoduck (Panopea globosa) and the Black Sea Cucumber (Holothuria atra) for invertebrates, the Spiny butterfly ray (Gymnura altavela) among elasmobranches, and the Black-and-yellow rockfish (Sebastes chrysomelas) for bony fishes. This study provides a first screening of the many species potentially affected by fisheries, prioritizes marine species for future research and management efforts, identifies the main data gaps, and sets the baseline for future research efforts and management. Furthermore, the results could improve market-based approaches like eco-labeling initiatives and the Responsible Seafood Consumption Guide, developed by Mexican authorities in collaboration with Comunidad and Biodiversidad (COBI, a civil society organization), to inform consumers about the origin and sustainability of fishery products.

Background: Controversy exists in the literature regarding the possible association between infertility treatments in singleton pregnancies and long-term risk for childhood malignancy. Data regarding infertility treatments in twins and long-term childhood malignancies are scarce. Objective: We sought to investigate whether twins conceived following infertility treatments are at an increased risk for childhood malignancy. Study design: A population-based retrospective cohort study, comparing the risk for future childhood malignancy in twins conceived by infertility treatments (in vitro fertilization and ovulation induction) and those who were conceived spontaneously. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. A Kaplan–Meier survival curve was used to compare the cumulative incidence of childhood malignancies, and a Cox proportional hazards model was constructed to control for confounders. Results: During the study period, 11,986 twins met the inclusion criteria; 2910 (24.3%) were born following infertility treatments. No statistically significant differences were noted between the groups comparing the rate (per 1000) of childhood malignancies (2.0 in the infertility treatments group vs. 2.2 in the comparison group, OR 1.04, 95% CI 0.41–2.62; p = 0.93). Likewise, the cumulative incidence over time was comparable between the groups (log-rank test, p = 0.87). In a Cox regression model, controlling for maternal and gestational age, no significant differences in childhood malignancies were noted between the groups (adjusted HR = 0.82, 95% CI 0.49–1.39, p = 0.47). Conclusions: In our population, twins conceived following infertility treatments are not at an increased risk for childhood malignancies.

This study aimed to describe nutritional and lifestyle parameters following one-anastomosis gastric bypass (OAGB). A multicenter study among OAGB patients across Israel (n = 277) and Portugal (n = 111) was performed. Patients were approached according to the time elapsed since surgery. An online survey with information regarding demographics, anthropometrics, and nutritional and lifestyle aspects was administered in both countries simultaneously. Respondents from Israel (pre-surgery age of 41.6 ± 11.0 years, 75.8% females) and Portugal (pre-surgery age of 45.6 ± 12.3 years, 79.3% females) reported changes in their appetite (≤94.0% and ≤94.6%), changes in their taste (≤51.0 and ≤51.4%), and intolerance to specific foods (i.e., red meat, pasta, bread, and rice). Bariatric surgery-related eating recommendations were generally followed well, but a trend toward lower adherence was evident in groups with longer time elapsed since surgery in both countries. Most respondents from Israel and Portugal reported participation in follow-up meetings with a surgeon (≤94.0% and 100%) and a dietitian (≤92.6% and ≤100%), while far fewer reported participation in any follow-up meeting with a psychologist/social worker (≤37.9% and ≤56.1%). Patients following OAGB might experience changes in appetite, taste, and intolerance to specific foods. Adherence to bariatric surgery-related eating recommendations is not always satisfying, especially in the longer term post-surgery.

Background: Primary Sjögren’s syndrome (pSS) is an autoimmune exocrinopathy characterized by lymphocytic infiltration, glandular dysfunction and systemic manifestations. Lyp protein is a negative regulator of the T cell receptor encoded by the tyrosine phosphatase nonreceptor-type 22 (PTPN22) gene. Multiple single-nucleotide polymorphisms (SNPs) in the PTPN22 gene have been associated with susceptibility to autoimmune diseases. This study aimed to investigate the association of PTPN22 SNPs rs2488457 (−1123 G>C), rs33996649 (+788 G>A), rs2476601 (+1858 C>T) with pSS susceptibility in Mexican mestizo subjects. Methods: One hundred fifty pSS patients and 180 healthy controls (HCs) were included. Genotypes of PTPN22 SNPs were identified by PCR-RFLP. PTPN22 expression was evaluated through RT–PCR analysis. Serum anti-SSA/Ro and anti-SSB/La levels were measured using an ELISA kit. Results: Allele and genotype frequencies for all SNPs studied were similar in both groups (p > 0.05). pSS patients showed 17-fold higher expression of PTNP22 than HCs, and mRNA levels correlated with SSDAI score (r2 = 0.499, p = 0.008) and levels of anti-SSA/Ro and anti-SSB/La autoantibodies (r2 = 0.200, p = 0.03 and r2 = 0.175, p = 0.04, respectively). Positive anti-SSA/Ro pSS patients expressed higher PTPN22 mRNA levels (p = 0.008), with high focus scores by histopathology (p = 0.02). Moreover, PTPN22 expression had high diagnostic accuracy in pSS patients, with an AUC = 0.985. Conclusions: Our findings demonstrate that the PTPN22 SNPs rs2488457 (−1123 G>C), rs33996649 (+788 G>A) and rs2476601 (+1858 C>T) are not associated with the disease susceptibility in the western Mexican population. Additionally, PTPN22 expression may be helpful as a diagnostic biomarker in pSS.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

PurposesMost molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.Patients and MethodsWe collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes.ResultsPAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors.ConclusionsThis is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America.Clinical Trial RegistrationClinicalTrials.gov (Identifier: NCT02326857).

Comprehensive data sets for lower-limb kinematics and kinetics during slope walking and running are important for understanding human locomotion neuromechanics and energetics and may aid the design of wearable robots (e.g., exoskeletons and prostheses). Yet, this information is difficult to obtain and requires expensive experiments with human participants in a gait laboratory. This study thus presents an empirical mathematical model that predicts lower-limb joint kinematics and kinetics during human walking and running as a function of surface gradient and stride cycle percentage. In total, 9 males and 7 females (age: 24.56 ± 3.16 years) walked at a speed of 1.25 m/s at five surface gradients (-15%, -10%, 0%, +10%, +15%) and ran at a speed of 2.25 m/s at five different surface gradients (-10%, -5%, 0%, +5%, +10%). Joint kinematics and kinetics were calculated at each surface gradient. We then used a Fourier series to generate prediction equations for each speed’s slope (3 joints x 5 surface gradients x [angle, moment, mechanical power]), where the input was the percentage in the stride cycle. Next, we modeled the change in value of each Fourier series’ coefficients as a function of the surface gradient using polynomial regression. This enabled us to model lower-limb joint angle, moment, and power as functions of the slope and as stride cycle percentages. The average adjusted R2 for kinematic and kinetic equations was 0.92 ± 0.18. Lastly, we demonstrated how these equations could be used to generate secondary gait parameters (e.g., joint work) as a function of surface gradients. These equations could be used, for instance, in the design of exoskeletons for walking and running on slopes to produce trajectories for exoskeleton controllers or for educational purposes in gait studies.

Introduction: Weight bias, stigma, and discrimination are common among healthcare professionals. We aimed to evaluate whether an online education module affects weight bias and knowledge about obesity in a private medical center setting. Methods: An open-label randomized controlled trial was conducted among all employees of a chain of private medical centers in Israel (n=3,290). Employees who confirmed their consent to participate in the study were randomized into intervention or control (i.e., 'no intervention') arms. The study intervention was an online 15-minute educational module that included obesity, weight bias, stigma, and discrimination information. Questionnaires on Anti-Fat Attitudes ('AFA'), fat-phobia ('F-scale), and beliefs about the causes of obesity were answered at baseline (i.e., right before the intervention), 7-days, and 30-days post-intervention. Results: A total of 506, 230, and 145 employees responded to the baseline, 7-day, and 30-day post-intervention questionnaires, respectively. Mean participant age was 43.3±11.6 years, 84.6% were women, and 67.4% held an academic degree. Mean F-scale scores and percentage of participants with above-average fat-phobic attitudes (≥3.6) significantly decreased only within the intervention group over time (P≤0.042). However, no significant differences between groups over time were observed for AFA scores or factors beliefs to cause obesity. Conclusions: A single exposure to an online education module on weight bias and knowledge about obesity may confer only a modest short-term improvement in medical center employees fat-phobic attitudes toward people with obesity. Future studies should examine if re-exposure to such intervention could impact weight bias, stigma, and discrimination among medical center staff in the long-term.

The kinetics of growth and α-amylase production of a novel Candida wangnamkhiaoensis yeast strain were studied in single-stage steady-state continuous cultures. This was performed in a split-cylinder internal-loop airlift bioreactor, using a variety of carbon sources as fermentation substrates. Results showed that the steady-state yields of cell mass from carbohydrates were practically constant for the range of dilution rates assayed, equaling 0.535 ± 0.030, 0.456 ± 0.033, and 0.491 ± 0.035 g biomass/g carbohydrate, when glucose, maltose, and starch, respectively were used as carbon sources. No α-amylase activity was detected when glucose was used as the carbon source in the influent medium, indicating that α-amylase synthesis of C. wangnamkhiaoensis is catabolically repressed by glucose. Contrastingly, maltose and starch induce synthesis of α-amylase in C. wangnamkhiaoensis, with starch being the best α-amylase inducer. The highest α-amylase volumetric and specific activities (58400 ± 800 U/L and 16900 ± 200 U/g biomass, respectively), and productivities (14000 ± 200 U/L·h and 4050 ± 60 U/g biomass·h, respectively) were achieved at a dilution rate of 0.24 h-1 using starch as the carbon source. In conclusion, single-stage steady-state continuous culture in an airlift bioreactor represents a powerful tool, both for studying the regulatory mechanisms of α-amylase synthesis by C. wangnamkhiaoensis and for α-amylase production. Furthermore, results showed that C. wangnamkhiaoensis represents a potential yeast species for the biotechnological production of α-amylase, which can be used for the saccharification of starch. This offers an attractive renewable resource for the production of biofuels (particularly bioethanol), representing an alternative to fossil fuels with reduced cost of substrates.

The kinetics of growth and α-amylase production of a novel Candida wangnamkhiaoensis yeast strain were studied in single-stage steady-state continuous cultures. This was performed in a split-cylinder internal-loop airlift bioreactor, using a variety of carbon sources as fermentation substrates. Results showed that the steady-state yields of cell mass from carbohydrates were practically constant for the range of dilution rates assayed, equaling 0.535 ± 0.030, 0.456 ± 0.033, and 0.491 ± 0.035 g biomass/g carbohydrate, when glucose, maltose, and starch, respectively were used as carbon sources. No α-amylase activity was detected when glucose was used as the carbon source in the influent medium, indicating that α-amylase synthesis of C. wangnamkhiaoensis is catabolically repressed by glucose. Contrastingly, maltose and starch induce synthesis of α-amylase in C. wangnamkhiaoensis, with starch being the best α-amylase inducer. The highest α-amylase volumetric and specific activities (58400 ± 800 U/L and 16900 ± 200 U/g biomass, respectively), and productivities (14000 ± 200 U/L·h and 4050 ± 60 U/g biomass·h, respectively) were achieved at a dilution rate of 0.24 h-1 using starch as the carbon source. In conclusion, single-stage steady-state continuous culture in an airlift bioreactor represents a powerful tool, both for studying the regulatory mechanisms of α-amylase synthesis by C. wangnamkhiaoensis and for α-amylase production. Furthermore, results showed that C. wangnamkhiaoensis represents a potential yeast species for the biotechnological production of α-amylase, which can be used for the saccharification of starch. This offers an attractive renewable resource for the production of biofuels (particularly bioethanol), representing an alternative to fossil fuels with reduced cost of substrates.

Comprehensive data sets for lower-limb kinematics and kinetics during slope walking and running are important for understanding human locomotion neuromechanics and energetics and may aid the design of wearable robots (e.g., exoskeletons and prostheses). Yet, this information is difficult to obtain and requires expensive experiments with human participants in a gait laboratory. This study thus presents an empirical mathematical model that predicts lower-limb joint kinematics and kinetics during human walking and running as a function of surface gradient and stride cycle percentage. In total, 9 males and 7 females (age: 24.56 ± 3.16 years) walked at a speed of 1.25 m/s at five surface gradients (-15%, -10%, 0%, +10%, +15%) and ran at a speed of 2.25 m/s at five different surface gradients (-10%, -5%, 0%, +5%, +10%). Joint kinematics and kinetics were calculated at each surface gradient. We then used a Fourier series to generate prediction equations for each speed's slope (3 joints x 5 surface gradients x [angle, moment, mechanical power]), where the input was the percentage in the stride cycle. Next, we modeled the change in value of each Fourier series' coefficients as a function of the surface gradient using polynomial regression. This enabled us to model lower-limb joint angle, moment, and power as functions of the slope and as stride cycle percentages. The average adjusted R2 for kinematic and kinetic equations was 0.92 ± 0.18. Lastly, we demonstrated how these equations could be used to generate secondary gait parameters (e.g., joint work) as a function of surface gradients. These equations could be used, for instance, in the design of exoskeletons for walking and running on slopes to produce trajectories for exoskeleton controllers or for educational purposes in gait studies.

BackgroundThe population of patients with cancer requiring palliative care (PC) is on the rise in India. Family caregivers will be essential members of the care team in the provision of PC.ObjectiveWe aimed to characterize provider perspectives of the challenges that Indian families face in taking on a palliative caregiving role.MethodData for this analysis came from an evaluation of the PC-PAICE project, a series of quality improvement interventions for PC in India. We conducted 44 in-depth semi-structured interviews with organizational leaders and clinical team members at seven geographically and structurally diverse settings. Through thematic content analysis, themes relating to the caregivers' role were identified using a combination of deductive and inductive approaches.ResultContextual challenges to taking up the PC caregiving role included family members' limited knowledge about PC and cancer, the necessity of training for caregiving responsibilities, and cultural preferences for pursuing curative treatments over palliative ones. Some logistical challenges include financial, time, and mental health limitations that family caregivers may encounter when navigating the expectations of taking on the caregiving role. Strategies to facilitate family buy-in for PC provision include adopting a family care model, connecting them to services provided by Non-Governmental Organizations, leveraging volunteers and social workers to foster PC awareness and training, and responding specifically to family's requests.ConclusionUnderstanding and addressing the various challenges that families face in adopting the caregiver role are essential steps in the provision and expansion of PC in India. Locally initiated quality improvement projects can be a way to address these challenges based on the context.

This essay provides an overview of the relationship between surveillance, individuals, and reality. To do this, I use a multilevel perspective that connects power (from agency to structure) to social systems theory. This novel approach means taking a holistic view on how individuals are managed beyond ideas of resistance and technology. At the agency level, individuals are constrained by continuous interactions through digital and behavioral exploitation. In the second meso-level, individuals attach to an informational system that renders, sorts, and distorts data fragments that resemble their ontology. Finally, at the structural level, more than being fragmented subjects, I argue that individuals and data constitute a new hermeneutic cycle in which reality itself is redefined in an autopoietic reading of things distanced from subjects and knowledge.

Abstract Backgroud In order to maximize In vitro fertilization (IVF) success rates in advanced- age patients, it has been suggested to favor the use of intracytoplasmic sperm injection (ICSI) over conventional insemination (CI), with the notion that ICSI would serve as a tool to overcome interference in sperm oocyte interaction and sperm oocyte penetration issues that can be related to maternal age and are not due to sperm abnormalities. We therefore aim to evaluate the role of ICSI in the treatment of non-male factor infertile patients aged ≥35 in terms of fertilization and top-quality embryo rates. Methods In this retrospective cohort study, data were collected and analyzed for all patients with non-male factor infertility, aged ≥35 treated, undergoing their first IVF cycle attempt with 6 or more oocytes yield, in whom a 50% ICSI-CI division was performed. Results Five hundreds and four oocytes were collected from 52 eligible patients. Overall, 245 oocytes underwent ICSI and 259 oocytes underwent CI. The fertilization rate was 71.0% following ICSI, compared to 50.1% in the CI treated oocytes (P

BackgroundHumans life histories have been described as "slow", patterned by slow growth, delayed maturity, and long life span. While it is known that human life history diverged from that of a recent common chimpanzee-human ancestor some ~4-8 mya, it is unclear how selection pressures led to these distinct traits. To provide insight, we compare wild chimpanzees and human subsistence societies in order to identify the age-specific vital rates that best explain fitness variation, selection pressures and species divergence.MethodsWe employ Life Table Response Experiments to quantify vital rate contributions to population growth rate differences. Although widespread in ecology, these methods have not been applied to human populations or to inform differences between humans and chimpanzees. We also estimate correlations between vital rate elasticities and life history traits to investigate differences in selection pressures and test several predictions based on life history theory.ResultsChimpanzees' earlier maturity and higher adult mortality drive species differences in population growth, whereas infant mortality and fertility variation explain differences between human populations. Human fitness is decoupled from longevity by postreproductive survival, while chimpanzees forfeit higher potential lifetime fertility due to adult mortality attrition. Infant survival is often lower among humans, but lost fitness is recouped via short birth spacing and high peak fertility, thereby reducing selection on infant survival. Lastly, longevity and delayed maturity reduce selection on child survival, but among humans, recruitment selection is unexpectedly highest in longer-lived populations, which are also faster-growing due to high fertility.ConclusionHumans differ from chimpanzees more because of delayed maturity and lower adult mortality than from differences in juvenile mortality or fertility. In both species, high child mortality reflects bet-hedging costs of quality/quantity tradeoffs borne by offspring, with high and variable child mortality likely regulating human population growth over evolutionary history. Positive correlations between survival and fertility among human subsistence populations leads to selection pressures in human subsistence societies that differ from those in modern populations undergoing demographic transition.

One anastomosis gastric bypass (OAGB) is an emerging bariatric procedure, yet data on its effect on the gastrointestinal tract are lacking. This study sought to evaluate the incidence of small-intestinal bacterial overgrowth (SIBO) following OAGB; explore its effect on nutritional, gastrointestinal, and weight outcomes; and assess post-OABG occurrence of pancreatic exocrine insufficiency (PEI) and altered gut microbiota composition. A prospective pilot cohort study of patients who underwent primary-OAGB surgery is here reported. The pre-surgical and 6-months-post-surgery measurements included anthropometrics, glucose breath-tests, biochemical tests, gastrointestinal symptoms, quality-of-life, dietary intake, and fecal sample collection. Thirty-two patients (50% females, 44.5 ± 12.3 years) participated in this study, and 29 attended the 6-month follow-up visit. The mean excess weight loss at 6 months post-OAGB was 67.8 ± 21.2%. The glucose breath-test was negative in all pre-surgery and positive in 37.0% at 6 months (p = 0.004). Positive glucose breath-test was associated with lower reported dietary intake and folate levels and higher vitamin A deficiency rates (p ≤ 0.036). Fecal elastase-1 test (FE1) was negative for all pre-surgery and positive in 26.1% at 6 months (p = 0.500). Both alpha and beta diversity decreased at 6 months post-surgery compared to pre-surgery (p ≤ 0.026). Relatively high incidences of SIBO and PEI were observed at 6 months post-OAGB, which may explain some gastrointestinal symptoms and nutritional deficiencies.

Lower-limb wearable robotic devices can improve clinical gait and reduce energetic demand in healthy populations. To help enable real-world use, we sought to examine how assistance should be applied in variable gait conditions and suggest an approach derived from knowledge of human locomotion mechanics to establish a 'roadmap' for wearable robot design. We characterized the changes in joint mechanics during walking and running across a range of incline/decline grades and then provide an analysis that informs the development of lower-limb exoskeletons capable of operating across a range of mechanical demands. We hypothesized that the distribution of limb-joint positive mechanical power would shift to the hip for incline walking and running and that the distribution of limb-joint negative mechanical power would shift to the knee for decline walking and running. Eight subjects (6M,2F) completed five walking (1.25 m s-1) trials at -8.53°, -5.71°, 0°, 5.71°, and 8.53° grade and five running (2.25 m s-1) trials at -5.71°, -2.86°, 0°, 2.86°, and 5.71° grade on a treadmill. We calculated time-varying joint moment and power output for the ankle, knee, and hip. For each gait, we examined how individual limb-joints contributed to total limb positive, negative and net power across grades. For both walking and running, changes in grade caused a redistribution of joint mechanical power generation and absorption. From level to incline walking, the ankle's contribution to limb positive power decreased from 44% on the level to 28% at 8.53° uphill grade (p < 0.0001) while the hip's contribution increased from 27% to 52% (p < 0.0001). In running, regardless of the surface gradient, the ankle was consistently the dominant source of lower-limb positive mechanical power (47-55%). In the context of our results, we outline three distinct use-modes that could be emphasized in future lower-limb exoskeleton designs 1) Energy injection: adding positive work into the gait cycle, 2) Energy extraction: removing negative work from the gait cycle, and 3) Energy transfer: extracting energy in one gait phase and then injecting it in another phase (i.e., regenerative braking).

El objetivo de este artículo es analizar cómo la militarización y el legalismo de las instituciones policiales brasileñas afectan su rol y la gestión de la criminalidad en Brasil. Esta característica doble del sistema brasileño mantendría una funcionalidad que regula, de forma cualitativa, la proporcionalidad del uso de la fuerza y la capacidad de procesar delitos ante la Justicia. Se verifica cómo esas estructuras se mantuvieron desde el inicio de la Nueva República, y se concluye que la militarización y el legalismo de los cuerpos de seguridad policial siguen imprimiendo los límites de la acción gubernamental mientras se amplifican salidas individualistas y conservacionistas como horizontes meta-políticos para tratar la criminalidad.

Abstract Background CD40 is a transmembrane protein mainly expressed on the antigen‐presenting cells surface. CD40 plays a crucial role in immunoglobulin class switching and antibodies production. Genetic polymorphisms in the CD40 gene have been associated with increased risk of systemic lupus erythematosus (SLE) in several populations. This study aimed to evaluate the association of CD40 polymorphisms (−1 C > T, rs1883832 and 6,048 G > T, rs4810485) with SLE susceptibility, as well as with mRNA expression and soluble CD40 (sCD40) levels. Methods The study included 293 patients with SLE and 294 control subjects (CS). Genotyping was performed by PCR‐RFLP method. CD40 mRNA expression was determined by quantitative real‐time PCR, and ELISA quantified sCD40 levels. Results The CD40 polymorphisms −1 C > T and 6,048 G > T were associated with SLE susceptibility. There was no difference between CD40 mRNA expression and CD40 polymorphisms. The sCD40 levels were lower in SLE patients with TT haplotype, whereas higher sCD40 levels were associated with damage and impaired renal function according to SLICC and KDIGO. The sCD40 levels were negatively correlated with eGFR. Conclusion The CD40 gene polymorphisms increase the risk of SLE in the western Mexican population. The sCD40 levels are associated with −1 C > T polymorphism and chronic kidney disease.

RNA levels in post-mortem tissue can differ greatly from those before death. Studying the effect of post-mortem interval on the transcriptome in 36 human tissues, Ferreira et al. find that the response to death is largely tissue-specific and develop a model to predict time since death based on RNA data.

Beauveria bassiana is an entomopathogenic fungus that is used for the biological control of different agricultural pest insects. B. bassiana is traditionally cultivated in submerged fermentation and solid-state fermentation systems to obtain secondary metabolites with antifungal activity and infective spores. This work presents the design and characterization of a new laboratory-scale biofilm bioreactor for the simultaneous production of oosporein and aerial conidia by B. bassiana PQ2. The reactor was built with materials available in a conventional laboratory. KLa was determined at different air flows (1.5–2.5 L/min) by two different methods in the liquid phase and in the exhaust gases. The obtained values showed that an air flow of 2.5 L/min is sufficient to ensure adequate aeration to produce aerial conidia and secondary metabolites by B. bassiana. Under the conditions studied, a concentration of 183 mg oosporein per liter and 1.24 × 109 spores per gram of support was obtained at 168 h of culture. These results indicate that the biofilm bioreactor represents a viable alternative for the production of products for biological control from B. bassiana.

En el presente trabajo se diseñó un sistema de instrumentación para medir la potencia producida por un generador de energía eléctrica en W-h. Las variables que se midieron en el sistema fueron: voltaje, corriente eléctrica y velocidad. El sistema está constituido por un sensor divisor de voltaje FZ0430 que mide el voltaje que entra a la batería proveniente del generador, un sensor de corriente ACS712, el cual mide la intensidad de la corriente eléctrica entre el positivo (+) de la batería y el positivo (+) del generador y un sensor V1-SENSORVE para detectar la velocidad dinámica; el cual se activa cuando empieza a funcionar el generador de energía eléctrica. Se realizó un programa bajo la plataforma de Arduino para la adquisición de los datos, análisis y procesamiento de la información de los 3 sensores, mostrando la velocidad y potencia generada en un display LCD de 162.