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Background: Gastric sensorimotor disorders (functional dyspepsia [FD] and gastroparesis [GP]) are prevalent and burdensome. Prolonged ambulatory recording using a wireless patch may provide novel information in these patients., Methods: Consecutive adult patients (age ≥ 18 years) referred for gastric emptying scintigraphy (GES) were eligible for study inclusion. Patients were excluded if they had prior foregut surgery; were taking opioids or other medications known to affect gastric emptying; had a HgbA1C > 10; or were recently hospitalized. Three wireless motility patches were applied to the skin prior to GES. Patients wore the patches for 6 days while recording meals, symptoms, and bowel movements using an iPhone app., Key Results: Twenty-three consecutive adults (87% women; mean age = 43.9 years; mean BMI = 26.7 kg/m 2 ) were enrolled. A gastric histogram revealed three levels of gastric myoelectric activity: weak, moderate, and strong. Patients with delayed gastric emptying at 4 h had weak gastric myoelectrical activity. Patients with nausea and vomiting had strong intestinal activity. Those with FD had weak gastric and intestinal myoelectric activity, and a weak meal response in the stomach, intestine, and colon compared to those with nausea alone or vomiting alone., Conclusions and Inferences: Patients with FD, and those with delayed gastric emptying, had unique gastrointestinal myoelectrical activity patterns. Reduced postprandial pan-intestinal myoelectric activity may explain the symptoms of FD in some patients. Recording gastrointestinal activity over a prolonged period in the outpatient setting has the potential to identify unique pathophysiologic patterns and meal-related activity that distinguishes patients with distinct gastric sensorimotor disease states., (© 2024 John Wiley & Sons Ltd.)

Background: Stomach, small intestine, and colon have distinct patterns of contraction related to their function to mix and propel enteric contents. In this study, we aim to measure gut myoelectric activity in the perioperative course using external patches in an animal model., Methods: Four external patches were placed on the abdominal skin of female Yucatan pigs to record gastrointestinal myoelectric signals for 3 to 5 d. Pigs subsequently underwent anesthesia and placement of internal electrodes on stomach, small intestine, and colon. Signals were collected by a wireless transmitter. Frequencies associated with peristalsis were analyzed for both systems for 6 d postoperatively., Results: In awake pigs, we found frequency peaks in several ranges, from 4 to 6.5 cycles per minute (CPM), 8 to 11 CPM, and 14 to 18 CPM, which were comparable between subjects and concordant between internal and external recordings. The possible effect of anesthesia during the 1 or 2 h before surgical manipulation was observed as a 59% (±36%) decrease in overall myoelectric activity compared to the immediate time before anesthesia. The myoelectrical activity recovered quickly postoperatively. Comparing the absolute postsurgery activity levels to the baseline for each pig revealed higher overall activity after surgery by a factor of 1.69 ± 0.3., Conclusions: External patch measurements correlated with internal electrode recordings. Anesthesia and surgery impacted gastrointestinal myoelectric activity. Recordings demonstrated a rebound phenomenon in myoelectric activity in the postoperative period. The ability to monitor gastrointestinal tract myoelectric activity noninvasively over multiple days could be a useful tool in diagnosing gastrointestinal motility disorders., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We present an algorithm to estimate the excited states of a quantum system by variational Monte Carlo, which has no free parameters and requires no orthogonalization of the states, instead transforming the problem into that of finding the ground state of an expanded system. Arbitrary observables can be calculated, including off-diagonal expectations, such as the transition dipole moment. The method works particularly well with neural network ansätze, and by combining this method with the FermiNet and Psiformer ansätze, we can accurately recover excitation energies and oscillator strengths on a range of molecules. We achieve accurate vertical excitation energies on benzene-scale molecules, including challenging double excitations. Beyond the examples presented in this work, we expect that this technique will be of interest for atomic, nuclear, and condensed matter physics.

Background: Cardiovascular diseases (CVDs) account for 17.9 million deaths annually. Behavioral risk factors increase the risk of dying from CVD. Air pollution is not included in this risk calculation since the appreciation of air pollution as a modifiable risk factor is still limited. The purpose of this study was to analyze CVD mortality attributed to air pollution in all World Health Organization WHO member states and demonstrate the association of CVD mortality with air pollution depending on countries' income level., Methods: The CVD death rate was calculated by dividing the number of deaths by the total population. The proportion of the population with primary reliance on clean fuels and technologies for cooking was calculated as an indicator of household air pollution. The annual mean concentration of fine particulate matter ≤2.5 µg/m 3  and ≤10.0 µg/m 3  to which the population is exposed was used as an indicator of ambient air pollution., Results: There is a gradual increase in CVD mortality attributed to air pollution from high-income countries (HICs) to low-income countries (LICs). Household air pollution is the major cause of CVD mortality in LICs. Ischemic heart disease mortality attributed to ambient air pollution in all countries is higher than stroke mortality attributed to ambient air pollution. In LIC, mortality from stroke is attributed to household air pollution of 39.27 ± 14.47, which is more than twice the stroke mortality attributed to ambient air pollution at 18.60 ± 5.64, t  = 7.17, p  < 0.01., Conclusion: Air pollution control should be an essential component of the CVD preventive strategy, along with lifestyle modifications and effective disease management., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Chronic Diseases and Translational Medicine published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

Background: COVID-19 pandemic represented a shock for healthcare systems. Italy was one of the first country to deal with a huge number of patients to be diagnosed, isolated, and treated with scarce evidence-based guidelines and resources. Several organizational and structural changes were needed to face the pandemic at local level. The article aims at studying the perceived impact of the newly implemented District Operation Centres (DOCs) of Local Health Authority (LHA) Roma 1 in managing active surveillance and home care of COVID-19 patients and their close contacts in cooperation with general practitioners (GPs)., Methods: A questionnaire, developed according to Delphi methodology, was validated by 7 experts and administered to a randomized sample of GPs and family paediatricians (FPs). All medical doctors selected received a phone interview between December 2020 and January 2021. The questionnaire investigated general characteristics of the sample, relations with DOC and its usefulness, and potential developments. A descriptive analysis was performed and inferential statistical tests were used to assess differences., Results: In April 2020 the LHA Roma 1 implemented one DOCs in each local health district. 215 medical doctors were interviewed, reaching the sample target for health districts (80% CL and 10% MOE) and the whole LHA (90% CL and 5% MOE). Several aspects in the management of COVID-19 cases and close contacts of COVID-19 cases, and of the support of DOCs to GPs/FPs were investigated. More than 55% of the GPs and FPs interviewed found the DOCs useful and more than 78% would recommend a service DOC-like to other LHAs. The medical professionals interviewed would use DOCs in the future as support in treating vulnerable patients, utilizing digital health tools, enlisting specialist doctors, establishing networks, and facilitating professional counselling by nurses., Conclusions: This study is an attempt to evaluate an organizational change happened during COVID-19 pandemic. DOCs were created to support GPs and FPs as a link between primary healthcare and public health. Although several difficulties were disclosed, DOCs' experience can help to overcome the fragmentation of the systems and the duality between primary care and public health and make the system more resilient., (© 2023. The Author(s).)

Background: Non-communicable diseases (NCDs) are major cause of death all over the world killing 41 million of the 57 million deaths (72%) in 2016. According to World Health Organization (WHO) Director General the biggest decrease in NCD mortality between 2000 and 2019 globally were for chronic respiratory diseases (CRDs) a 37% decline. The WHO Western Pacific Region (WPRO) made the biggest gains against CRD a 55.9% drop. We analysed CRD mortality in the WPRO comparing with other WHO regions., Methods: Assessment of the risk factors was made in all WHO countries mainly in 2016. Lifestyle modifications concerning tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol in 2020. We used WHO assessment of ambient and household air pollution attributable to chronic obstructive pulmonary disease (COPD) mortality., Results: WPRO comprises 27 countries, 10 high-income countries (HIC) and 17 middle-income countries (MIC). A total of 52 countries in other WHO regions belong to HIC and 86 countries to MIC. No difference was found in the tobacco demand-reduction measures. Clear difference was demonstrated in the prevalence of the raised blood pressure (RBP) which was lower in the WPRO. In the WPRO HIC every fifth has RBP while in other regions it was every forth. Similar difference was observed for MIC. COPD mortality linked to air pollution was twice higher in the WPRO. It was highest in MIC. CRD management probably plays a crucial role in the decline of the observed mortality in the region since numerous WHO global, regional and national prevention and management CRD approaches and activities have been successfully initiated and implemented there. WHO Global Alliance against Chronic Respiratory Diseases (GARD) was successfully initiated in Beijing in 2006. Two subsequent global GARD meetings held in Seoul [2007] and Beijing [2019] had a tremendous impact on the CRD awareness, prevention and control strategies in the region. These events have stimulated development of the national CRD programmes. Beijing's declaration "Call for action for lung health" stressed the better management of CRD at primary healthcare level., Conclusions: Better RBP control, improved prevention, diagnosis and treatment of CRD could contribute to the observed decline of premature CRD mortality in the region., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1466/coif). The series “GARD Section” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Sleep is vital for most animals, yet its mechanism and function remain unclear. We found that permeability of the BBB (blood-brain barrier)-the organ required for the maintenance of homeostatic levels of nutrients, ions, and other molecules in the brain-is modulated by sleep deprivation (SD) and can cell-autonomously effect sleep changes. We observed increased BBB permeability in known sleep mutants as well as in acutely sleep-deprived animals. In addition to molecular tracers, SD-induced BBB changes also increased the penetration of drugs used in the treatment of brain pathologies. After chronic/genetic or acute SD, rebound sleep or administration of the sleeping aid gaboxadol normalized BBB permeability, showing that SD effects on the BBB are reversible. Along with BBB permeability, RNA levels of the BBB master regulator moody are modulated by sleep. Conversely, altering BBB permeability alone through glia-specific modulation of moody, gαo, loco, lachesin , or neuroglian -each a well-studied regulator of BBB function-was sufficient to induce robust sleep phenotypes. These studies demonstrate a tight link between BBB permeability and sleep and indicate a unique role for the BBB in the regulation of sleep.

Light-activated drugs are a promising way to localize biological activity and minimize side effects. However, their development is complicated by the numerous photophysical and biological properties that must be simultaneously optimized. To accelerate the design of photoactive drugs, we describe a procedure that combines ligand-protein docking with chemical property prediction based on machine learning (ML). We apply this procedure to 58 proteins and 9000 photo-drug candidates based on azobenzene cis-trans isomerism. We find that most proteins display a preference for trans isomers over cis and that the binding affinities of nominally active/inactive pairs are in fact highly correlated. These findings have significant value for photopharmacology research, and reinforce the need for virtual screening to identify compounds with rare desirable properties. Further, we combine our procedure with quantum chemical validation to identify promising candidates for the photoactive inhibition of PARP1, an enzyme that is over-expressed in cancer cells. The top compounds are predicted to have long-lived active forms, differential bioactivity, and absorption in the near-infrared therapeutic window.

Background and Aims: Limited means exist to assess gastrointestinal activity in a noninvasive, objective way that is highly predictive of underlying motility disorders. The aim of this paper is to demonstrate the feasibility of recording myoelectric gastrointestinal activity by cutaneous patches and to correlate myoelectric signals with gastrointestinal function in various clinical settings., Methods: A novel wireless patch system (WPS) (G-Tech Medical) that acquires gastrointestinal myoelectrical signals was placed on the patients' anterior abdomens. Data were transmitted wirelessly to a mobile device with a user interface and forwarded to a cloud server where processing algorithms identified episodes of motor activity, quantified their parameters, and nominally assigned them to specific gastrointestinal organs based on their frequencies., Results: The inherent reproducibility of the WPS measurement technique itself and from the underlying gut activity, coupled with source validation and sensitivity to changes in gut activity in several physiologic and pathologic states, demonstrates its feasibility, safety, and performance in clinical settings., Conclusions: The novel WPS technology, measuring myoelectric intestinal activity noninvasively and continuously over multiple days, is feasible in a wide range of clinical settings, highlighting its promise in the diagnosis and management of motility disorders. Further research is required for more extensive validation and to determine how best to employ this information to optimize patient care., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Molecular photoswitches are the foundation of light-activated drugs. A key photoswitch is azobenzene, which exhibits trans - cis isomerism in response to light. The thermal half-life of the cis isomer is of crucial importance, since it controls the duration of the light-induced biological effect. Here we introduce a computational tool for predicting the thermal half-lives of azobenzene derivatives. Our automated approach uses a fast and accurate machine learning potential trained on quantum chemistry data. Building on well-established earlier evidence, we argue that thermal isomerization proceeds through rotation mediated by intersystem crossing, and incorporate this mechanism into our automated workflow. We use our approach to predict the thermal half-lives of 19,000 azobenzene derivatives. We explore trends and trade-offs between barriers and absorption wavelengths, and open-source our data and software to accelerate research in photopharmacology., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Noncommunicable diseases (NCDs) place a heavy burden on populations globally and in particular, on lower-income countries (LIC). WHO identified a package of 16 "best buy" lifestyle and management interventions that are cost-effective and applicable in all settings. The purpose of this study was to evaluate and compare NCD risk factors in all WHO countries and make preliminary assessment of "best buy" interventions., Methods: Risk factors estimation was made in 188 countries. NCD attributable "best buys" concern tobacco use, unhealthy diet, physical inactivity, and harmful use of alcohol. Management issues are based on the availability of the national NCD guidelines and provision of drug therapy., Results: Every fourth adult in high-income countries (HIC) has raised blood pressure (RBP). Prevalence of RBP in lower-middle-income countries (LMIC) and LIC is 22%-23% (HIC/LMIC: t  =  3.12 , p  <  0.01 ). Prevalence of diabetes in LIC is less than half of that in HIC and upper-middle-income countries (UMIC) UMIC/LIC: t = 8.37 , p < 0.001 . Obesity prevalence is gradually decreasing from HIC to LIC (HIC/LIC: t = 11.48 , p < 0.001 ). Highest level of physical inactivity is seen in HIC, which then gradually declines to LIC (17%). Tobacco prevalence in LIC is almost less than half of that in HIC and UMIC (HIC/LIC: t = 7.2 , p < 0.0001 ). There is a gradual decline in the implementation of "best buys" from HIC to LIC., Conclusion: Wealthier countries have better implementation of the WHO NCD prevention strategy., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Chronic Diseases and Translational Medicine published by John Wiley & Sons, Ltd on behalf of Chinese Medical Association.)

Introduction: Currently, there is no accurate noninvasive measurement system to diagnose gastrointestinal (GI) motility disorders. Wireless skin patches have been introduced to provide an accurate noninvasive measurement of GI myoelectric activity which is essential for developing neuro-stimulation devices to treat GI motility disorders. The aim of this study is to compare the external and internal electrical signal measurements in ambulatory pigs., Methods: Yucatan pigs underwent placement of internal electrodes on the stomach, small intestine, and colon. Wires were brought through the abdominal wall. Signals were collected by a wireless receptor. Four external patches were placed on the abdominal skin to record the signals simultaneously. Pigs were kept for 6 d while the sensors were continuously recording the data from both systems., Results: Internal sensors detected rich signals from each organ. The stomach had a dominant frequency that ranged from 4 to 4.5 cpm, with occasional higher frequencies at 2, 3 and 4 times that. Small intestine signals had their primary energy in the 12-15 cpm range. Colon signals primarily displayed a dominant broad peak in the 4-6 cpm region. External skin patches detected a substantial fraction of the activities measured by the internal electrodes. A clear congruence in the frequency spectrum was observed between the internal and external readings., Conclusions: Internally measured myoelectrical signals confirmed different patterns of rhythmic activity of the stomach, small intestine, and colon. Skin patches provided GI myoelectric measurement with a range of frequencies that could be useful in the diagnosis and treatment of motility disorders., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease (CVD) is the major noncommunicable disease (NCD) accounting for 17.9 million deaths. If current trends continue, the annual number of deaths from CVD will rise to 22.2 million by 2030. The United Nations General Assembly adopted a sustainable development goal (SDG) by 2030 to reduce NCD mortality by one-third. The purpose of this study was to analyze the CVD mortality trends in different countries implementing World Health Organization (WHO) NCD Action Plan and emphasize effective ways to achieve SDG., Methods: WHO statistics, based on the Member-States unified mortality and causes-of-death reports were used for analyzing trends and different interventions., Results: Reduction of CVD mortality from 2000 to 2016 in 49 countries was achieved for stroke at 43% and ischemic heart disease at 30%. Smoking prevalence and raised blood pressure (RBP) decreased in 84% and 55% of the countries. Eighty-nine percent of high-income countries (HIC) demonstrated a decline in tobacco smoking against 67% in middle-income countries (MIC). Sixty-nine percent of HIC demonstrated a decline in RBP against 15% in MIC. CVD management, tobacco, and unhealthy diet reduction measures are significantly better in HIC. The air pollution level was higher in MIC., Conclusion: Building partnerships between countries could enhance their efforts for CVD prevention and successful achievement of SDG., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Chronic Diseases and Translational Medicine published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

Light-induced chemical processes are ubiquitous in nature and have widespread technological applications. For example, photoisomerization can allow a drug with a photo-switchable scaffold such as azobenzene to be activated with light. In principle, photoswitches with desired photophysical properties like high isomerization quantum yields can be identified through virtual screening with reactive simulations. In practice, these simulations are rarely used for screening, since they require hundreds of trajectories and expensive quantum chemical methods to account for non-adiabatic excited state effects. Here we introduce a diabatic artificial neural network (DANN), based on diabatic states, to accelerate such simulations for azobenzene derivatives. The network is six orders of magnitude faster than the quantum chemistry method used for training. DANN is transferable to azobenzene molecules outside the training set, predicting quantum yields for unseen species that are correlated with experiment. We use the model to virtually screen 3100 hypothetical molecules, and identify novel species with high predicted quantum yields. The model predictions are confirmed using high-accuracy non-adiabatic dynamics. Our results pave the way for fast and accurate virtual screening of photoactive compounds., (© 2022. The Author(s).)

Machine learning (ML) outperforms traditional approaches in many molecular design tasks. ML models usually predict molecular properties from a 2D chemical graph or a single 3D structure, but neither of these representations accounts for the ensemble of 3D conformers that are accessible to a molecule. Property prediction could be improved by using conformer ensembles as input, but there is no large-scale dataset that contains graphs annotated with accurate conformers and experimental data. Here we use advanced sampling and semi-empirical density functional theory (DFT) to generate 37 million molecular conformations for over 450,000 molecules. The Geometric Ensemble Of Molecules (GEOM) dataset contains conformers for 133,000 species from QM9, and 317,000 species with experimental data related to biophysics, physiology, and physical chemistry. Ensembles of 1,511 species with BACE-1 inhibition data are also labeled with high-quality DFT free energies in an implicit water solvent, and 534 ensembles are further optimized with DFT. GEOM will assist in the development of models that predict properties from conformer ensembles, and generative models that sample 3D conformations., (© 2022. The Author(s).)

To accommodate daily recurring environmental changes, animals show cyclic variations in behaviour and physiology, which include prominent behavioural states such as sleep-wake cycles but also a host of less conspicuous oscillations in neurological, metabolic, endocrine, cardiovascular and immune functions. Circadian rhythmicity is created endogenously by genetically encoded molecular clocks, whose components cooperate to generate cyclic changes in their own abundance and activity, with a periodicity of about a day. Throughout the body, such molecular clocks convey temporal control to the function of organs and tissues by regulating pertinent downstream programmes. Synchrony between the different circadian oscillators and resonance with the solar day is largely enabled by a neural pacemaker, which is directly responsive to certain environmental cues and able to transmit internal time-of-day representations to the entire body. In this Review, we discuss aspects of the circadian clock in Drosophila melanogaster and mammals, including the components of these molecular oscillators, the function and mechanisms of action of central and peripheral clocks, their synchronization and their relevance to human health.

Chirality and molecular conformation are central components of life: biological systems rely on stereospecific interactions between discrete (macro)molecular conformers, and the impacts of stereochemistry and rigidity on the properties of small molecules and biomacromolecules have been intensively studied. Nevertheless, how these features affect the properties of synthetic macromolecules has received comparably little attention. Here we leverage iterative exponential growth and ring-opening metathesis polymerization to produce water-soluble, chiral bottlebrush polymers (CBPs) from two enantiomeric pairs of macromonomers of differing rigidity. Remarkably, CBPs with conformationally flexible, mirror image side chains show several-fold differences in cytotoxicity, cell uptake, blood pharmacokinetics and liver clearance; CBPs with comparably rigid, mirror image side chains show no differences. These observations are rationalized with a simple model that correlates greater conformational freedom with enhanced chiral recognition. Altogether, this work provides routes to the synthesis of chiral nanostructured polymers and suggests key roles for stereochemistry and conformational rigidity in the design of future biomaterials., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The COVID-19 pandemic called for a reorganisation of the methods for providing health services. The aim of this paper is to describe the organisational model implemented by one of Rome's Local Health Units (LHU), ASL Roma 1, for the "at-home COVID-19 vaccination campaign" dedicated to a target population and to outline data related to vaccination coverage stratified by health districts. A cross-sectional study was designed to describe the strategies implemented by LHU to deliver at-home vaccination programmes. People eligible for the at-home vaccination programme included patients living in the area of the LHU, being assisted by the district home care centre or not transportable or individuals with social situations that make traveling difficult. Priority for vaccination was given to (I) age > 80 years, (II) ventilated patients with no age limit, (III) very seriously disabled people with no age limit. Patients' data were acquired from regional and LHU databases. From 5 February until the 16 May, 6127 people got at least one dose of Pfizer-Biontech Comirnaty ® vaccine, while 5278 (86.14%) completed the necessary two doses. The highest number of vaccines was administered during the first week of April, reaching 1296 doses overall. The number of vaccines administered were similar across the districts. The average number of people vaccinated at home was 6 per 1000 inhabitants in the LHU. This model proved to be extremely complex but effective, reaching satisfying results in terms of vaccination coverage.

Objectives: Dialectical behaviour therapy (DBT) emphasizes generalization of skills to the patient's real-world context as a primary mechanism of change in treatment. To promote generalization, DBT includes weekly skills-focused homework assignments and as-needed phone coaching. Despite this central function of generalization in DBT, research on these treatment components is limited. The current study addresses this research gap by assessing the association of homework and phone coaching to DBT treatment outcomes., Design: A longitudinal study design explored the extent to which (a) completion of skills homework and (b) frequency of phone coaching were associated with therapeutic changes and treatment outcomes in a DBT intensive outpatient programme (DBT-IOP)., Method: Medical records and diary cards of 56 patients who had completed a four-month treatment cycle of DBT-IOP were reviewed and coded for proportion of skills homework completed, frequency of phone coaching calls, and reported urges for and engagement in suicide, non-suicidal self-injury, illicit or non-prescribed substance use, and alcohol use behaviours., Results: Completion of skills homework and frequency of phone coaching were significantly associated with (a) reduced urges for suicide, non-suicidal self-injury, illicit or non-prescribed substance use, and alcohol use from the beginning to end of treatment and (b) a lower likelihood of engaging in any of these behaviours during the final month of treatment., Conclusions: Results suggest that within a DBT programme modified for an intensive outpatient setting, skills homework and phone coaching may enhance therapeutic change and outcomes in target behaviours. These generalization methods appear to be important ingredients of DBT effectiveness., Practitioner Points: In dialectical behaviour therapy (DBT), therapeutic skills homework and phone coaching are specifically designed to promote generalization of skills from the therapeutic context to the patient's real-world contexts. In a DBT intensive outpatient programme, patient engagement with therapeutic homework and phone coaching were associated with favourable therapeutic change and outcomes in target urges and behaviours. Clinicians may consider a patient's lack of homework completion and/or phone coaching to be early warning signs of poor therapeutic progress within dialectical behaviour therapy., (© 2021 The British Psychological Society.)

Carbohydrate-binding proteins (lectins) play vital roles in cell recognition and signaling, including pathogen binding and innate immunity. Thus, targeting lectins, especially those on the surface of immune cells, could advance immunology and drug discovery. Lectins are typically oligomeric; therefore, many of the most potent ligands are multivalent. An effective strategy for lectin targeting is to display multiple copies of a single glycan epitope on a polymer backbone; however, a drawback to such multivalent ligands is they cannot distinguish between lectins that share monosaccharide binding selectivity (e.g., mannose-binding lectins) as they often lack molecular precision. Here, we describe the development of an iterative exponential growth (IEG) synthetic strategy that enables facile access to synthetic glycomacromolecules with precisely defined and tunable sizes up to 22.5 kDa, compositions, topologies, and absolute configurations. Twelve discrete mannosylated "glyco-IEGmers" are synthesized and screened for binding to a panel of mannoside-binding immune lectins (DC-SIGN, DC-SIGNR, MBL, SP-D, langerin, dectin-2, mincle, and DEC-205). In many cases, the glyco-IEGmers had distinct length, stereochemistry, and topology-dependent lectin-binding preferences. To understand these differences, we used molecular dynamics and density functional theory simulations of octameric glyco-IEGmers, which revealed dramatic effects of glyco-IEGmer stereochemistry and topology on solution structure and reveal an interplay between conformational diversity and chiral recognition in selective lectin binding. Ligand function also could be controlled by chemical substitution: by tuning the side chains of glyco-IEGmers that bind DC-SIGN, we could alter their cellular trafficking through alteration of their aggregation state. These results highlight the power of precision synthetic oligomer/polymer synthesis for selective biological targeting, motivating the development of next-generation glycomacromolecules tailored for specific immunological or other therapeutic applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: According to the World Health Organization (WHO), a global reduction of 17% has been achieved in the major noncommunicable disease-associated mortality rate since 2000. This decline was due to the decreasing mortality associated with cardiovascular and chronic respiratory diseases. The WHO has not made any comments on diabetes-related mortality thus far. The objective of this study was to demonstrate trends in diabetes-related mortality associated with country-wide interventions., Methods: The WHO statistics were used to assess trends in diabetes-related mortality from 2000 to 2016. Different types of community-based interventions in 49 countries were compared and assessed., Results: The baseline mortality decreased by 7%. Mortality in middle-income countries was higher than that in high-income countries. The prevalence of obesity showed a gradual increase in all countries. After implementation of the WHO "best buy" in 2010, mortality increased in 17 countries and decreased in 32 countries. Regarding the smoking prevalence trend, 87% countries with decreasing diabetes-related mortality had a gradual decline in tobacco usage since 2000. The decline was observed only in 43% countries with increasing diabetes-related mortality. The prevalence of hypertension increased in 19% countries with declining diabetes-related mortality and in 35% countries with increasing diabetes-related mortality. Physical activity measures tended to be better implemented in countries with declining diabetes-related mortality than in countries with increasing diabetes-related mortality., Conclusion: Smoking cessation and better blood pressure control are associated with declining diabetes-related mortality. Longer implementation periods are needed for other lifestyle interventions., Competing Interests: None., (© 2021 Chinese Medical Association. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Computer simulations can provide mechanistic insight into ionic liquids (ILs) and predict the properties of experimentally unrealized ion combinations. However, ILs suffer from a particularly large disparity in the time scales of atomistic and ensemble motion. Coarse-grained models are therefore used in place of costly all-atom simulations, accessing longer time scales and larger systems. Nevertheless, constructing the many-body potential of mean force that defines the structure and dynamics of a coarse-grained system can be complicated and computationally intensive. Machine learning shows great promise for the linked challenges of dimensionality reduction and learning the potential of mean force. To improve the coarse-graining of ILs, we present a neural network model trained on all-atom classical molecular dynamics simulations. The potential of mean force is expressed as two jointly trained neural network interatomic potentials that learn the coupled short-range and many-body long range molecular interactions. These interatomic potentials treat temperature as an explicit input variable to capture its influence on the potential of mean force. The model reproduces structural quantities with high fidelity, outperforms the temperature-independent baseline at capturing dynamics, generalizes to unseen temperatures, and incurs low simulation cost.

Competing Interests: The authors have declared that no competing interests exist.

Background: According to the Independent High-level Commission on Non-communicable Diseases (NCD) of the World Health Organization (WHO), global reduction in lung cancer mortality has been achieved since the year 2000, although this effect is not sufficient to reach the 30% reduction of mortality from NCDs by the year 2030, as stipulated by the United Nations Sustainable Development Goal 3.4. The objective of this study was to analyze whether the lifestyle changes implemented by the WHO at country level could have an impact on mortality from this form of cancer., Methods: WHO statistics, based on the unified mortality and causes-of-death reports of Member-State countries, were used to evaluate global lung cancer mortality trends and make comparisons and assessments of different types of community-based, country-wide interventions., Results: The lung cancer mortality decline was associated with the anti-tobacco campaign initiated by the WHO in the last 15 to 20 years. Comprehensive tobacco control remained the major and most successful lifestyle modification measure. In countries with declining lung cancer mortality, 91% of countries had decreasing tobacco prevalence in males and 82% in females. Country- wide measures to increase physical activity had a strong tendency to be better implemented in countries with declining lung cancer mortality (t = 1.79, P > 0.05). Other WHO "best-buy" lifestyle modification campaigns (diet and alcohol) had been carried out for shorter periods, and their associations with lung cancer were less strong than tobacco. There was no significant difference between countries with declining and increasing lung cancer mortality in the measures for reduction of harmful alcohol use (t = 0.92, P > 0.05) and unhealthy diet reduction measures (t = 0.84, P > 0.05)., Conclusion: Following WHO "best-buys" should facilitate to move countries towards the NCD including lung cancer mortality reduction targets. Governments and communities must embrace these targets with coordinated effective action for better health.

Circadian rhythmicity of gene expression is a conserved feature of cell physiology. This involves fine-tuning between transcriptional and post-transcriptional mechanisms and strongly depends on the metabolic state of the cell. Together these processes guarantee an adaptive plasticity of tissue-specific genetic programs. However, it is unclear how the epigenome and RNA Pol II rhythmicity are integrated. Here we show that the PcG protein EZH1 has a gateway bridging function in postmitotic skeletal muscle cells. On the one hand, the circadian clock master regulator BMAL1 directly controls oscillatory behavior and periodic assembly of core components of the PRC2-EZH1 complex. On the other hand, EZH1 is essential for circadian gene expression at alternate Zeitgeber times, through stabilization of RNA Polymerase II preinitiation complexes, thereby controlling nascent transcription. Collectively, our data show that PRC2-EZH1 regulates circadian transcription both negatively and positively by modulating chromatin states and basal transcription complex stability., (© 2024. The Author(s).)

Purpose: Limited means exist to assess gastrointestinal activity in pediatric patients postoperatively. Recently, myoelectric gastrointestinal activity recorded by cutaneous patches has been shown in adult patients to be predictive of clinical return of gastrointestinal function postoperatively. The aim of this case series is to demonstrate the feasibility of this system in pediatric patients and to correlate myoelectric signals with return of bowel function clinically., Methods: Pediatric patients undergoing abdominal surgery were recruited to have wireless patches placed on the abdomen within two hours postoperatively. Myoelectric data were transmitted wirelessly to a mobile device with a user-interface and forwarded to a cloud server where processing algorithms identified episodes of motor activity, quantified their parameters and nominally assigned them to specific gastrointestinal organs based on their frequencies., Results: Three patients (ages 5 months, 4 year, 16 year) were recruited for this study. Multiple patches were placed on the older subjects, while the youngest had a single patch due to space limitations. Rhythmic signals of the stomach, small intestine, and colon could be identified in all three subjects. Patients showed gradual increase in myoelectric intestinal and colonic activity leading up to the first recorded bowel movement., Conclusion: Measuring myoelectric intestinal activity continuously using a wireless patch system is feasible in a wide age range of pediatric patients. The increase in activity over time correlated well with the patients' return of bowel function. More studies are planned to determine if this technology can predict return of bowel function or differentiate between physiologic ileus and pathologic conditions., Competing Interests: Conflict of Interest: Anand Navalgund, Lindsay Axelrod and Steve Axelrod are employees of G-Tech Medical. Patches for this study were supplied by G-Tech Medical. The other authors have no disclosures related to this work., (Copyright © 2019 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Many important open quantum systems, such as light harvesting systems irradiated with natural incoherent light, present challenging computational problems. Specifically, such systems are characterized by multiple time scales over many orders of magnitude. We describe and apply an efficient approach to determine rates and dynamics in such systems. As an example, we present a theoretical and computational analysis of retinal isomerization under incoherent solar excitation using a minimal retinal model. Solar- and bath-induced Fano coherences are shown to have a small but non-negligible effect on the reaction dynamics, and the effect of Fano coherences on the reaction rate is shown to depend strongly upon the form and strength of the system-bath coupling. Using the isomerization probability to obtain the time-dependent cellular hyperpolarization, we show that the effect of coherence on hyperpolarization dynamics is small compared to the effect of natural variations in the solar intensity.

Background: Passage of flatus after abdominal surgery signals resolution of physiological postoperative ileus (POI) and often, particularly after complex open surgeries, serves as the trigger to initiate oral feeding. To date, there is no objective tool that can predict time to flatus allowing for timely feeding and optimizing recovery. In an open, prospective study, we examine the use of a noninvasive wireless patch system that measures electrical activity from gastrointestinal smooth muscles in predicting time to first flatus., Methods: Eighteen patients who underwent open abdominal surgery at El Camino Hospital, Mountain View, CA, were consented and studied. Immediately following surgery, wireless patches were placed on the patients' anterior abdomen. Colonic frequency peaks in the spectra were identified in select time intervals and the area under the curve of each peak times its duration was summed to calculate cumulative myoelectrical activity., Results: Patients with early flatus had stronger early colonic activity than patients with late flatus. At 36 h post-surgery, a linear fit of time to flatus vs cumulative colonic myoelectrical activity predicted first flatus as much as 5 days (± 22 h) before occurrence., Conclusions: In this open, prospective pilot study, noninvasive measurement of colon activity after open abdominal surgery was feasible and predictive of time to first flatus. Interventions such as feeding can potentially be optimized based on this prediction, potentially improving outcomes, decreasing length of stay, and lowering costs.

Postoperative delayed gastric emptying (DGE) is a frustrating complication of pancreaticoduodenectomy (PD). We studied whether monitoring of postoperative gastric motor activity using a novel wireless patch system can identify patients at risk for DGE. Patients ( n = 81) were prospectively studied since 2016; 75 patients total were analyzed for this study. After PD, battery-operated wireless patches (G-Tech Medical) that acquire gastrointestinal myoelectrical signals are placed on the abdomen and transmit data by Bluetooth. Patients were divided into early and late groups by diet tolerance of 7 days [enhanced recovery after surgery (ERAS) goal]. Subgroup analysis was done of patients included after ERAS initiation. The early and late groups had 50 and 25 patients, respectively, with a length of stay (LOS) of 7 and 11 days ( P < 0.05). Nasogastric insertion was required in 44% of the late group. Tolerance of food was noted by 6 versus 9 days in the early versus late group ( P < 0.05) with higher cumulative gastric myoelectrical activity. Diminished gastric myoelectrical activity accurately identified delayed tolerance to regular diet in a logistical regression analysis [area under the curve (AUC): 0.81; 95% confidence interval (CI), 0.74-0.92]. The gastric myoelectrical activity also identified a delayed LOS status with an AUC of 0.75 (95% CI, 0.67-0.88). This stomach signal continued to be predictive in 90% of the ERAS cohort, despite earlier oral intake. Measurement of gastric activity after PD can distinguish patients with shorter or longer times to diet. This noninvasive technology provides data to identify patients at risk for DGE and may guide the timing of oral intake by gastric "readiness." NEW & NOTEWORTHY Limited clinical indicators exist after pancreaticoduodenectomy to allow prediction of delayed gastric emptying (DGE). This study introduces a novel, noninvasive, wireless patch system capable of accurately monitoring gastric myoelectric activity after surgery. This system can differentiate patients with longer or shorter times to a regular diet as well as provide objective data to identify patients at risk for DGE. This technology has the potential to individualize feeding regimens based on gastric activity patterns to improve outcomes.

In many important cases, the rate of excitation of a system embedded in an environment is significantly smaller than the internal system relaxation rates. An important example is that of light-induced processes under natural conditions, in which the system is excited by weak, incoherent (e.g., solar) radiation. Simulating the dynamics on the time scale of the excitation source can thus be computationally intractable. Here we describe a method for obtaining the dynamics of quantum systems without directly solving the master equation. We present an algorithm for the numerical implementation of this method and, as an example, use it to reconstruct the internal conversion dynamics of pyrazine excited by sunlight. Significantly, this approach also allows us to assess the role of quantum coherence on biological time scales, which is a topic of ongoing interest.