Effects of spatial configuration and fundamental frequency on speech intelligibility in multiple-talker conditions in the ipsilateral horizontal plane and median planea).

Spatial separation and fundamental frequency (F0) separation are effective cues for improving the intelligibility of target speech in multi-talker scenarios. Previous studies predominantly focused on spatial configurations within the frontal hemifield, overlooking the ipsilateral side and the entire median plane, where localization confusion often occurs. This study investigated the impact of spatial and F0 separation on intelligibility under the above-mentioned underexplored spatial configurations. The speech reception thresholds were measured through three experiments for scenarios involving two to four talkers, either in the ipsilateral horizontal plane or in the entire median plane, utilizing monotonized speech with varying F0s as stimuli. The results revealed that spatial separation in symmetrical positions (front-back symmetry in the ipsilateral horizontal plane or front-back, up-down symmetry in the median plane) contributes positively to intelligibility. Both target direction and relative target-masker separation influence the masking release attributed to spatial separation. As the number of talkers exceeds two, the masking release from spatial separation diminishes. Nevertheless, F0 separation remains as a remarkably effective cue and could even facilitate spatial separation in improving intelligibility. Further analysis indicated that current intelligibility models encounter difficulties in accurately predicting intelligibility in scenarios explored in this study.

CD38 deficiency promotes skeletal muscle and brown adipose tissue energy expenditure through activating NAD+-Sirt1-PGC1α signaling pathway.

Obesity is a metabolic syndrome characterized by abnormal lipid deposition and energy imbalance. CD38 is a single-chain transmembrane glycoprotein widely expressed in a variety of cell types. The roles of skeletal muscle and brown fat in CD38 deficiency under HFD-induced obesity remain unknown. In this study, we established obesity model with HFD and examined the changes in metabolites with metabonomics. Our results showed that CD38 expression was increased in muscle and brown fat after HFD treatment. Moreover, the results of metabonomics showed that CD38 deficiency significantly altered the metabolites in energy metabolism, cofactor generation, and redox homeostasis. Furthermore, CD38 deficiency reduced the expressions of NADPH oxidase 2 and FASN in mRNA level. We found that the expressions of Sirt1, Sirt3, and PGC1α were upregulated in CD38-deficient muscle tissue. In brown fat, the Sirt1-3, cell death inducing DFFA-like effector A, ELOVL3, and Dio2 expressions were increased in CD38-deficient mice. Our results showed the uncoupling protein 1 expression was upregulated. And NAD+ supplementation increased the expression of Sirt1 and PGC1α after palmitic acid treatment. Taken together, our results demonstrated that the protection of CD38 deficiency on HFD-induced obesity was related to the inhibition of oxidative stress and increasing energy expenditure via activating NAD+/Sirtuins signaling pathways in muscle and brown fat.

CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis.

Diabetic cardiomyopathy is one of the diabetes mellitus-induced cardiovascular complications that can result in heart failure in severe cases, which is characterized by cardiomyocyte apoptosis, local inflammation, oxidative stress, and myocardial fibrosis. CD38, a main hydrolase of NAD+ in mammals, plays an important role in various cardiovascular diseases, according to our previous studies. However, the role of CD38 in diabetes-induced cardiomyopathy is still unknown. Here, we report that global deletion of the CD38 gene significantly prevented diabetic cardiomyopathy induced by high-fat diet plus streptozotocin (STZ) injection in CD38 knockout (CD38-KO) mice. We observed that CD38 expression was up-regulated, whereas the expression of Sirt3 was down-regulated in the hearts of diabetic mice. CD38 deficiency significantly promoted glucose metabolism and improved cardiac functions, exemplified by increased left ventricular ejection fraction and fractional shortening. In addition, we observed that CD38 deficiency markedly decreased diabetes or high glucose and palmitic acid (HG + PA)-induced pyroptosis and apoptosis in CD38 knockout hearts or cardiomyocytes, respectively. Furthermore, we found that the expression levels of Sirt3, mainly located in mitochondria, and its target gene FOXO3a were increased in CD38-deficient hearts and cardiomyocytes with CD38 knockdown under diabetic induction conditions. In conclusion, we demonstrated that CD38 deficiency protected mice from diabetes-induced diabetic cardiomyopathy by reducing pyroptosis and apoptosis via activating NAD+/Sirt3/FOXO3a signaling pathways.

Covalent Metalloporphyrin Polymer Coated on Carbon Nanotubes as Bifunctional Electrocatalysts for Water Splitting.

Metalloporphyrins have exhibited excellent electrocatalytic activities for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). In order to improve the efficiency and conductivity, these molecular catalysts need to be immobilized on conductive electrode materials. Herein, a facile "one-pot" strategy was developed to coat a covalent metalloporphyrin polymer on a carbon nanotube (CNT) as bifunctional catalysts [denoted as MTIPP@CNTs, H2TIPP = 5,10,15,20-tetra(4-(imidazole-1-yl)phenyl)porphyrin)] for water splitting in alkaline solution. MTIPP@CNTs have shown excellent electrocatalytic activities for both the HER and OER when metalloporphyrin's central metal is optimized as well as the amount of catalysts that is loaded on the CNT. The overpotential (η10) of NiTIPP@CNT-2 for the OER is only 320 mV at a current density of 10 mA cm-2 in 1.0 M KOH, and CoTIPP@CNT-1 exhibited an excellent electrocatalytic activity for the HER (η10 = 450 mV for 10 mA cm-2). Furthermore, the remarkable bifunctional electrocatalytic performance (a cell voltage of 2.04 V with a current density of 10 mA cm-2) was also explored in the overall water splitting test.

Physical and oxidative stability of astaxanthin microcapsules prepared with liposomes.

BACKGROUND: Oil bodies (OBs) are a kind of natural and stable oil nucleate microcapsule in which the triglyceride matrix can be used as an appropriate carrier of hydrophobic molecules. Astaxanthin has high antioxidant properties but is extremely sensitive to oxidation, causing the loss of its bioactive properties. RESULTS: The purpose of this study was to clarify the effects of environmental factors (light, oxygen, temperature, and pH) on the physical and oxidative stability of astaxanthin microcapsules prepared with peanut oil bodies (POBs). After 14 days of storage, the retention rate of astaxanthin in peanut oil microcapsules (POMs) was significantly increased. The astaxanthin retention rate of POMs stored under light conditions was higher than under dark conditions. Similarly, the retention rate of astaxanthin in POMs was significantly increased during vacuum storage. The astaxanthin retention rate was also the highest when POMs were stored at 4 °C, whereas it was the lowest at pH 3.0. CONCLUSION: The experiment demonstrated that microcapsulation could improve the astaxanthin retention rate and storage stability, and recombinant OBs were potential ideal wall materials for astaxanthin embedding. © 2022 Society of Chemical Industry.

Bone marrow cells are differentiated into MDSCs by BCC-Ex through down-regulating the expression of CXCR4 and activating STAT3 signalling pathway.

Studies showed that the increase of myeloid-derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour-derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)-secreted exosomes (BCC-Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour-bearing mice and BCC-Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC-Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs-related functional proteins Arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC-Ex significantly down-regulated the expressions of chemokine receptor CXCR4 and markedly up-regulated the levels of inflammatory cytokines IL-6 and IL-10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC-Ex, indicating that BCC-Ex-induced MDSCs might be dependent on the down-regulation of CXCR4. Western blot showed that BCC-Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs.

Path Planning of Mobile Robots Based on a Multi-Population Migration Genetic Algorithm.

In the field of robot path planning, aiming at the problems of the standard genetic algorithm, such as premature maturity, low convergence path quality, poor population diversity, and difficulty in breaking the local optimal solution, this paper proposes a multi-population migration genetic algorithm. The multi-population migration genetic algorithm randomly divides a large population into several small with an identical population number. The migration mechanism among the populations is used to replace the screening mechanism of the selection operator. Operations such as the crossover operator and the mutation operator also are improved. Simulation results show that the multi-population migration genetic algorithm (MPMGA) is not only suitable for simulation maps of various scales and various obstacle distributions, but also has superior performance and effectively solves the problems of the standard genetic algorithm.

The enhanced affinity of moderately hydrolyzed whey protein to EGCG promotes the isoelectric separation and unlocks the protective effects on polyphenols.

The instability and discoloration of (-)-epigallocatechin-3-gallate (EGCG) constrain its application in functional dairy products. Concurrently, challenges persist in the separation and utilization of whey in the dairy industry. By harnessing the interactions between polyphenols and whey proteins or their hydrolysates, this study proposed a method that involved limited enzymatic hydrolysis followed by the addition of EGCG and pH adjustment around the isoelectric point to obtain whey protein hydrolysates (WPH)-EGCG. Over 92 % of protein-EGCG complexes recovered from whey while ensuring the preservation of α-lactalbumin. The combination between EGCG and WPH depended on hydrogen bonding and hydrophobic interactions, significantly enhanced the thermal stability and storage stability of EGCG. Besides, the intestinal phase retention rate of EGCG in WPH-EGCG complex was significantly increased by 23.67 % compared to free EGCG. This work represents an exploratory endeavor in the improvement of EGCG stability and expanding the utilization approaches of whey.

Potential impact of climate change on the distribution of Capricornis milneedwardsii, a vulnerable mammal in China.

Climate change significantly impacted on the survival, development, distribution, and abundance of living organisms. The Chinese serow Capricornis milneedwardsii, known as the "four unlike," is a Class II nationally protected species in China. In this study, we predicted the geographical suitability of C. milneedwardsii under current and future climatic conditions using MaxEnt. The model simulations resulted in area under the receiver operating characteristic curve (AUC) values above 0.9 for both current and future climate scenarios, indicating the excellent performance, high accuracy, and credibility of the MaxEnt model. The results also showed that annual precipitation (Bio12), slope, elevation, and mean temperature of wettest quarter (Bio8) were the key environmental variables affecting the distribution of C. milneedwardsii, with contributions of 31.2%, 26.4%, 11%, and 10.3%, respectively. The moderately and highly suitable habitats were mainly located in the moist area of China, with a total area of 34.56 × 104 and 16.61 × 104 km2, respectively. Under future climate change scenarios, the areas of suitability of C. milneedwardsii showed an increasing trend. The geometric center of the total suitable habitats of C. milneedwardsii would show the trend of northwest expansion and southeast contraction. These findings could provide a theoretical reference for the protection of C. milneedwardsii in the future.

Successful endotracheal intervention for primary tracheal acinic cell carcinoma: A case report and literature review.

INTRODUCTION: Primary tracheal acinic cell carcinoma (ACC) is an exceptionally rare malignancy, posing challenges in understanding its clinical behavior and optimal management. Surgical resection has traditionally been the primary treatment modality, but we present a compelling case of tracheal ACC managed with endotracheal intervention, challenging conventional approaches. PATIENT CONCERNS: A 53-year-old woman presented with shortness of breath, cough, and hemoptysis. Enhanced computed tomography revealed an obstructive tracheal lesion, leading to her referral for further assessment. DIAGNOSIS: Microscopic evaluation, immunohistochemistry, and clinical assessments confirmed primary tracheal ACC, an exceedingly rare condition with limited clinical insights. INTERVENTIONS: We utilized rigid bronchoscopy to perform endotracheal intervention, successfully resecting the tumor and restoring tracheal patency. Postoperatively, the patient received no radiotherapy or chemotherapy. OUTCOMES: The patient achieved complete recovery, with 24-month follow-up examinations indicating no recurrence or metastatic disease. Only minimal scar tissue remained at the resection site. CONCLUSION: This case demonstrates the potential of endotracheal intervention as a curative approach for primary tracheal ACC, minimizing invasiveness and preserving tracheal function. Collaborative research efforts and extensive case reporting are crucial for advancing our understanding of this rare malignancy and optimizing treatment strategies for improved patient outcomes.

A versatile bilayer smart packaging based on konjac glucomannan/alginate for maintaining and monitoring seafood freshness.

This study introduces a novel multi-functional double-layer intelligent packaging. It focuses on developing a dual-function system capable of real-time monitoring and freshness preservation. Specifically, cellulose nanocrystalline (CNC) was obtained through acid hydrolysis, and then CNC/soybean protein isolate (CNC/SPI) complex colloid particles were prepared via antisolvent method. These particles served as stabilizers to prepare oil-in-water (O/W) cinnamon essential oil Pickering emulsion (CSCEO). The CSCEO was then integrated into the emulsified hydrophobic layer of a konjac glucomannan (Kgm) matrix through intermolecular hydrogen bonding. Finally, alginate (Alg) matrix containing alizarin (Al) as an indicator was added to construct the bilayer structure using a layer-by-layer casting strategy. The inner layer Alg/Al was the pH/NH3-responsive indicator layer, while the outer layer Kgm/CSCEO acted as the high-barrier bacteriostatic layer. The obtained dual-function, double-layer film (Alg/Al-Kgm/CSCEO), which possesses a sensitive, reversible and rapid response towards pH/NH3, shows exceptional antibacterial and antioxidant properties, as well as excellent mechanical property, light-blocking capability and hydrophobicity. For monitoring and maintaining the actual freshness of shrimp, such a bilayer packaging displays smallest change of ∆E and TVB-N (18.65 mg/100 g) even after 72 h, which further highlighting its potential in enhancing food safety and extending shelf life.

The function of long non-coding RNA IFNG-AS1 in autoimmune diseases.

The prevalence of autoimmune diseases ranks as the third most common disease category globally, following cancer and heart disease. Numerous studies indicate that long non-coding RNA (lncRNA) plays a pivotal role in regulating human growth, development, and the pathogenesis of various diseases. It is more than 200 nucleotides in length and is mostly involve in the regulation of gene expression. Furthermore, lncRNAs are crucial in the development and activation of immune cells, with an expanding body of research exploring their association with autoimmune disorders in humans. LncRNA Ifng antisense RNA 1 (IFNG-AS1), a key regulatory factor in the immune system, also named NeST or TMEVPG1, is proximally located to IFNG and participates in the regulation of it. The dysregulation of IFNG-AS1 is implicated in the pathogenesis of several autoimmune diseases. This study examines the role and mechanism of IFNG-AS1 in various autoimmune diseases and considers its potential as a therapeutic target.

LncRNA XIST: A Breakthrough in Inflammation-related Diseases.

BACKGROUND: Long non-coding RNA (LncRNA) is a type of non-coding RNA that plays an important role in the body and accounts for the majority of RNA, and this non-coding RNA can regulate disease onset and progression with its wide range of functions. LncRNA Xist, also known as the long non-coding RNA X inactive specific transcript, is a member of them. It can regulate the development of organismal diseases by acting downstream on specific target genes. In addition to this, it can also influence disease onset and progression by acting on apoptosis, migration, invasion, and other processes. It has been shown that XIST plays an important role in the development of inflammation. OBJECTIVE: To explore the role played by XIST in inflammation-related diseases and to explore its mechanism of action. METHODS: This paper summarizes and analyzes the role played by XIST in inflammation- related diseases by conducting a search in PubMed. CONCLUSION: In this paper, we summarize the mechanism of action of XIST in different types of inflammation-related diseases and propose new protocols for the future clinical treatment of these diseases.

LncRNA Gm15232 Promotes Lipogenesis in Aging Mice Through the miR-192-3p/GCR Pathway.

Recent scientific studies have highlighted the importance of long-chain noncoding RNAs (lncRNAs) in a variety of metabolic diseases, but the specific functions and mechanisms of lncRNAs in aberrant lipid synthesis associated with aging are unknown. In this work, we inspected the effects of lncRNAs on the lipid metabolism in aging mice, as substantial evidence suggests that aging disturbs lipid metabolism. The results revealed that the expression of lncRNA Gm15232 was significantly elevated in the epididymal white adipose tissue of aging mice compared to adult mice. This upregulation of Gm15232 functioned as a competitive endogenous RNA by inhibiting the expression of miR-192-3p, and the ensuing downregulation of miR-192-3p increased the expression of the glucocorticoid receptor gene, which ultimately stimulated fat synthesis. The upregulation of Gm15232 thus increased lipogenesis through this mechanism. This study reveals a potential target for the treatment of age-related abnormalities of lipid metabolism.

Enzymatically green-produced bacterial cellulose nanoparticle-stabilized Pickering emulsion for enhancing anthocyanin colorimetric performance of versatile films.

To enhance the colorimetric performance of anthocyanin (Ant), a konjac glucomannan (KGM)-based multifunctional pH-responsive indicator film was fabricated by introducing enzymatically prepared bacterial nanocellulose (EBNC) stabilized camellia oil/camellia essential oil Pickering emulsion (BCCE). Specifically, optimized enzymatic hydrolysis time (36 h) was determined based on the particle size and microstructure. Then BCCE (containing 0.4% EBNC) was incorporated into Ant-containing KGM, and the novel active indicator film (KGM-Ant-BCCE) was constructed. Films with varying BCCE concentrations (3%-11%) exhibited enhanced UV shielding, thermal stability, mechanical strength, water vapor and oxygen permeability, hydrophobicity, and antioxidant performance. The pronounced color change of KGM-Ant-BCCE indicated its potential for visually detecting shrimp freshness. Moreover, the biodegradability (25 days) confirmed the environmentally benign property of the film. In summary, incorporating green-produced EBNC nanoparticle-stabilized BCCE offers an innovative pathway to improve the color indication capability of polysaccharide-based smart packaging.

Polysaccharides from Balanophora harlandii Hook: Isolation, characterization, and anti-inflammation activities.

Balanophora harlandii Hook (B. harlandii), a folk medicine, has been traditionally employed to treat traumatic bleeding, gastroenteritis, icteric hepatitis, hemorrhoids, and other conditions. In this work, polysaccharides with anti-inflammatory effects were extracted from B. harlandii and purified. The extraction conditions were optimized, and the properties of one purified neutral fraction, denoted as BHPs-W-S3, were analyzed. BHPs-W-S3 has a molecular weight of 14.1 kDa, and its three main monosaccharides are glucose, galactose, and xylose, with a molar ratio of 6.4:1.7:1.1. Its main chain consists of →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →6)-ß-D-Galp-(1→, →3,6)-ß-D-Galp-(1→, and it has branch chains at the O-4 and/or O-3 positions. In addition, in vitro experiments showed that the polysaccharides from B. harlandi can decrease the phosphorylation level of p65 and IκBα in LPS-induced RAW264.7 cells to reduce the expression of the pro-inflammatory genes such as TNF-α, IL-6, and IL-1ß.

Mapping knowledge domains for mine heat hazard: a bibliometric analysis of research trends and future needs.

As the shallow mineral resources are nearly depleted, the mining of deep resources has become an urgent problem to be studied. The increase in mine depth can lead to the increase of mine heat hazard, which is a critical concern for mining safety/occupational health and safety. However, there are limited review articles available regarding the prevention of mine heat hazard. To fill in this gap, a bibliometric analysis and knowledge mapping of the field of mine heat hazard prevention are presented in this paper. A total of 314 papers from the Web of Science (WOS) core collection database that published between January 1998 and July 2022 were analyzed using VOSviewer and CiteSpace. China, South Africa, Poland, USA, and Australia are the top five countries in this field. The important journals are Applied Thermal Engineering, Applied Energy, Energies, and International Journal of Mining Science and Technology. In addition, the research focal points and two research fronts were identified and discussed. The knowledge base of mine heat hazard research focuses on mine cooling technology, energy efficiency optimization of cooling systems, thermodynamic theory, and occupational health. There are two research fronts. One is to use the numerical simulation method to study various problems such as simulate the performance of refrigeration systems and thermal comfort in mines. The second is to study the occupational health impact of climate change on miners. Therefore, this paper provides readers and academics with an overview of the intellectual structure and knowledge body that have been developed on the subject of mine heat hazard.

Mapping the knowledge domain of microbial desulfurization application in fuels and ores for sustainable industry.

Direct application of high-sulfur fuels and ores can cause environmental pollution (such as air pollution and acid rain) and, in serious cases, endanger human health and contribute to property damage. In the background of preserving the environment, microbial desulfurization technologies for high-sulfur fuels and ores are rapidly developed. This paper aims to reveal the progress of microbial desulfurization research on fuels and ores using bibliometric analysis. 910 publications on microbial desulfurization of fuels and ores from web core databases were collected in this work, spanning 39 years. Through 910 retrieved documents, collaborative networks of authors, institutions and countries were mapped by this work, the sources of highly cited articles and cited documents were statistically analyzed, and keyword development from different perspectives was discussed. The results of the study provide a reference for microbial desulfurization research and benefit environmental protection and energy green applications.

Characterization of the structural and mechanical properties of pinecone fish (Monocentris japonica) scales.

In this paper, the microstructure characteristics and mechanical properties (including nano-indentation, tensile, and penetration behaviors) of the scales from pinecone fish (Monocentris japonica) were investigated. The M. japonica scales display a unique hierarchical structure and consist of three layers: an outer bone layer with high mineralization, an intermediate bone layer with obvious pore structures, and an inner collagen layer composed of multiple plies of collagen fibers. The hardness and indentation modulus of the three structural layers exhibit gradient changes, and decrease gradually from the outer layer to the inner layer. Tensile tests show that the tensile response and failure modes of the scales are different under dry and hydrated conditions. The dry scales have higher tensile strength (46.35 MPa) and Young's modulus (0.74 GPa), while the hydrated scales exhibit higher ultimate strain (20.18%) and toughness (4.57 MPa). Penetration tests indicate that the scales have a significantly high resistance to penetration, and increase the penetration force by more than six times compared with the descaled skin. Furthermore, the structure-property relationship of the M. japonica scales was discussed. It is found that the hard outer layer and the porous intermediate layer help to disperse the stress, and the soft inner layer containing collagen fiber plies helps to deflect the crack propagation, which are responsible for the excellent mechanical properties of the scales. The outcome of this study can provide a valuable biomimetic design inspiration for lightweight and high-strength composite materials in engineering fields. RESEARCH HIGHLIGHTS: Microstructure characteristics and mechanical properties of the Monocentris japonica scales were investigated. The M. japonica scales can be divided into three layers rather than two layers. The M. japonica scales exhibited high tensile strength and penetration resistance.

Review on the Advancements of Stethoscope Types in Chest Auscultation.

Stethoscopes were originally designed for the auscultation of a patient's chest for the purpose of listening to lung and heart sounds. These aid medical professionals in their evaluation of the cardiovascular and respiratory systems, as well as in other applications, such as listening to bowel sounds in the gastrointestinal system or assessing for vascular bruits. Listening to internal sounds during chest auscultation aids healthcare professionals in their diagnosis of a patient's illness. We performed an extensive literature review on the currently available stethoscopes specifically for use in chest auscultation. By understanding the specificities of the different stethoscopes available, healthcare professionals can capitalize on their beneficial features, to serve both clinical and educational purposes. Additionally, the ongoing COVID-19 pandemic has also highlighted the unique application of digital stethoscopes for telemedicine. Thus, the advantages and limitations of digital stethoscopes are reviewed. Lastly, to determine the best available stethoscopes in the healthcare industry, this literature review explored various benchmarking methods that can be used to identify areas of improvement for existing stethoscopes, as well as to serve as a standard for the general comparison of stethoscope quality. The potential use of digital stethoscopes for telemedicine amidst ongoing technological advancements in wearable sensors and modern communication facilities such as 5G are also discussed. Based on the ongoing trend in advancements in wearable technology, telemedicine, and smart hospitals, understanding the benefits and limitations of the digital stethoscope is an essential consideration for potential equipment deployment, especially during the height of the current COVID-19 pandemic and, more importantly, for future healthcare crises when human and resource mobility is restricted.