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Investigation of multi-drug resistant Candida auris using species-specific molecular markers in immunocompromised patients from a tertiary care hospital in Quetta, Pakistan

Introduction Candida auris is an emerging multidrug-resistant pathogen responsible for nosocomial infections worldwide, characterized by high mortality rates and significant challenges in detection due to frequent misidentification. Classified by the WHO as a pathogen of critical importance since it exhibits resistance to multiple antifungal agents, particularly fluconazole, and is highly transmissible in healthcare settings. Conventional detection methods often lack the accuracy required for effective infection control. This study aimed to conduct inferential and molecular analyses of C. auris and other yeast species infecting immunocompromised patients in the Special and Intensive Care Units (SCU and ICU) of a tertiary care hospital in Quetta, Pakistan. In this region, C. auris remains rarely studied and is frequently misdiagnosed by clinical staff due to limited awareness and diagnostic challenges. Notably, no prior research has been conducted on C. auris in Quetta. The study also sought to develop reliable diagnostic methods suitable for resource-limited settings, addressing a critical gap in healthcare infrastructure. Materials and methods Samples (150 each) from the ear, axilla, groin, and saliva of SCU/ICU patients were collected and processed on yeast malt agar, with preliminary identification using Brilliance Candida Agar (BCA) and CHROMagar Candida Plus (CCP). Advanced techniques, including PCR amplification of ITS regions, DNA sequencing, RFLP with Msp1, MALDI-TOF, Vitek 2, and species-specific primers, were used for identification. Antifungal susceptibility to fluconazole, amphotericin B, and voriconazole were also assessed. Results The culture test revealed that 42.6% samples were positive for yeast infections. In addition to detecting Candida auris in 4 cultures, chromogenic media identified 6 other Candida species: C. albicans, C. dubliniensis, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis. Further validation through advanced techniques, including molecular diagnostics and MALDI-TOF, enabled the identification of additional species: C. famata, C. kefyr, C. lusitaniae, and Meyerozyma (Candida) guilliermondii. Out of all identified yeast species C. dubliniensis was the most common, followed by C. albicans and C. tropicalis, with the highest infection rates observed in saliva samples. Antifungal Susceptibility Tests (AST) revealed that C. auris isolates were resistant to Fluconazole, Amphotericin B, and Voriconazole, highlighting multidrug resistance. This study represents the first report of novel multidrug-resistant C. auris from Quetta, Pakistan, indicating that C. auris is prevalent among ICU and SCU patients. Novel species specific primers targeting phospholipase B, topoisomerase II, CDR and 18s genes were designed in our laboratory and not previously reported in earlier studies, proved highly effective for the rapid identification of Candida species. The established protocol using these primers is recommended for implementation in resource-limited laboratory settings. The statistical analysis demonstrated significant correlations between Candida species infection (dependent variable) and several independent factors (variables) emphasizing the importance of targeted diagnostics and intervention strategies.

Temporal trends in cardiovascular disease risk factors attributed burden in Iran, 1990–2021

Parathyroid near-infrared autofluorescence differently benefits depending on the surgeon’s skill for preventing from hypoparathyroidism after total thyroidectomy: A systematic review and meta-analysis

Objective To evaluate the role of parathyroid near-infrared autofluorescence in reducing the incidence of postoperative hypocalcemia and hypoparathyroidism after total thyroidectomy, and to determine which surgeons benefit most from parathyroid near-infrared autofluorescence use. Methods A literature search was conducted in PubMed, Web of Science, and the Cochrane Library databases for English-language articles published from June 2011 to October 31, 2023. The inclusion criteria were studies conducted on patients who underwent total thyroidectomy for benign or malignant thyroid pathologies, comparing postoperative parathyroid function between parathyroid near-infrared autofluorescence techniques and conventional surgery with data on calcium and/or parathyroid hormone levels. The exclusion criteria included: reviews, letters, meta-analyses, case reports, animal experiments, or basic research. Of the initial 387 articles retrieved, we included 14. A meta-analysis was performed to calculate the pooled odds ratio and weighted mean deviation with a random-effects model. Main outcomes were Calcium and parathyroid hormone levels after total thyroidectomy with or without parathyroid near-infrared autofluorescence use. Results Fourteen studies were included in the meta-analysis. Pooled odds ratios of temporary and permanent hypocalcemia were 0.56 (95% confidence interval 0.43–0.72) and 0.61 (95% confidence interval 0.33–1.13), respectively. Meta-regression analysis revealed that near-infrared autofluorescence benefits surgeons with the high incidence of temporary hypocalcemia by naked eye surgery (≥15%) by reducing temporary hypocalcemia (p = 0.0091) and skillful surgeons by increasing the number of autotransplanted parathyroid glands (p = 0.0225). Conclusions Parathyroid near-infrared autofluorescence has different benefits depending on the skill level of the surgeon.

A ternary encoding network fusing scale awareness and large kernel attention for camouflaged object detection

Quercetin alleviates cerebral ischemia and reperfusion injury in hyperglycemic animals by reducing endoplasmic reticulum stress through activating SIRT1

Hyperglycemia aggravates cerebral ischemic reperfusion injury (CIRI). Neuroprotective drugs that are effective in reducing CIRI in animals with normoglycemic condition are ineffective in ameliorating CIRI under hyperglycemic condition. This study investigated whether quercetin alleviates hyperglycemic CIRI by inhibiting endoplasmic reticulum stress (ERS) through modulating the SIRT1 signaling pathway. A middle cerebral artery occlusion/reperfusion (MCAO/R) model was induced in STZ-injected hyperglycemic rats. High glucose and oxygen glucose deprivation/reoxygenation (OGD/R) models were established in HT22 cells. The results demonstrated that hyperglycemia exacerbated CIRI, and quercetin pretreatment decreased the neurological deficit score and cerebral infarct volume, and alleviated neuron damage in the cortex of the penumbra in hyperglycemic MCAO/R rats, indicating that quercetin could be a candidate for treating hyperglycemic CIRI. Moreover, quercetin pretreatment reduced apoptosis, inhibited the expression of the ERS marker proteins GRP78 and ATF6, and mitigated the expression of the ERS-mediated proapoptotic protein CHOP in hyperglycemic MCAO/R rats, suggesting that quercetin alleviated hyperglycemic CIRI by inhibiting ERS and ERS-mediated apoptosis. Furthermore, quercetin upregulated Sirt1 expression in HG+OGD/R treated HT22 cells and inhibited PERK, p-eIF2α, ATF4, and CHOP expression. In contrast, the SIRT1 selective inhibitor EX-527 blocked the effect of quercetin on protein expression in the SIRT1/PERK pathway and aggravated HT22 cell injury. These findings indicate that quercetin inhibits ERS-mediated apoptosis through modulating the SIRT1 and PERK pathway. In conclusion, quercetin alleviates hyperglycemic CIRI by inhibiting ERS-mediated apoptosis through activating SIRT1 that consequently suppressed ERS signaling.

Author Correction: From the diagnosis of infectious keratitis to discriminating fungal subtypes; a deep learning-based study

Enhancement of YTHDF2 plays a protective role in acute IRI models through downregulation of TUG1 expression

As one of the major causes of acute kidney injury, renal ischemia-reperfusion is a common health problem in a series of clinical situations, including renal transplantation. Although the mechanisms of renal IRI have been widely investigated, effective strategies are still in lacking for its prevention and treatment. In previous study, we found that the down-regulation of taurine upregulated gene 1, a long non-coding RNA (lncRNA TUG1), markedly alleviated renal IRI through mitigating the cell inflammation and apoptosis. At meanwhile, YTHDF2, an RNA methylation reading protein, was identified as a vital player in IRI of distinct organs, however, not reported in kidney. We then conducted the current study on the function of YTHDF2 in renal IRI and its regulatory role to TUG1. Based on renal IRI models in vitro and in vivo, dramatical down-regulation of YTHDF2 was presented. Subsequently, exogenous perturbation of YTHDF2 was conducted and its protective effects on cell apoptosis were demonstrated in acute IRI exogenous. Furthermore, with the same model, it was indicated that YTHDF2 protein negative regulated TUG1 RNA via direction interaction. Since then, YTHDF2 was proved as a potential protector of renal IRI through restraining of TUG1. In further speculation, induction of YTHDF2 in IRI will possibly become a possible strategy to combat the pathological process post renal transplantation or other clinical conditions.

Host biomarkers and parasite biomass are associated with severe malaria in Mozambican children: a case–control study

Gender and cultural aspects of brucellosis transmission and management in Nakasongola cattle corridor in Uganda

Background Brucellosis is a zoonotic disease with significant public health and economic effects on societies. In Uganda, brucellosis is endemic and a primary contributor in livestock productivity losses. This is more worrisome for populations in the cattle corridor with high reliance on cattle and milk for nutritional value and symbol in social relations and identity. The community’s social construction may affect comprehension of brucellosis hence leading to exposure and increased vulnerability to transmission. Despite brucellosis’ high prevalence in the cattle corridor, little attention has been paid to its social construction. Hence, this study explored the interplay between gender dynamics, vulnerability and social construction of brucellosis transmission, in consideration of the unique socio-cultural context that characterizes cattle corridor populations. Methods Using an exploratory qualitative approach, the study was conducted in Nakasongola cattle corridor within three sub counties; Nabiswera, Nakitoma and Wabinyonyi using key informant interviews (KIIs) and focus group discussions (FGDs). Purposive sampling was used to identify participants for the four FGD [8–12] each from a subcounty though one was combined and 15 KIIs. Data were collected using face -to -face interviews with an interview guide that was structured using the Socio Ecological Model of Human Behaviour framework (SEMHB) constructs. Thematic analysis was conducted in NVivo 12 Pro incorporating both deductive (guided by the SEMHB) and inductive approaches (guided by the data). Findings The study identified important themes under each SEMHB influence level (Individual, Interpersonal, Community and Societal level). The study indicates that social composition and role distribution are driven by social and cultural expectations and significantly contribute to exposure and vulnerability to infection in the cattle corridor. For instance, it is paramount that women undergoing marriage preparations to be fed on raw milk for a certain period prior to their ceremony to enhance beauty. Also, important to note that use of personal protection to assist births is viewed by the community as opposing cultural norms, creating a perception of detachment from the highly valued cattle. Another noteworthy finding is the level of knowledge on brucellosis in terms of symptoms, transmission route, prevention and treatment at the interpersonal level. Furthermore, findings show practices such as the consumption of raw milk and assisted births, as being rooted in the social cultural norms, hence critical for transmission of brucellosis. At the community and organizational levels, the findings indicate an inadequate level of knowledge sharing and reluctance towards preventive measures as structural factors for the transmission of brucellosis and are ingrained in family and power relations. Conclusion The findings highlight that the social construction of brucellosis transmission is rooted in gender roles, social- cultural and power structures highlighting the influence of living process and spaces, at the different societal levels. Such complex dynamics play a critical role in determining individuals’ susceptibility to infection as well as transmission potential of the disease-causing agent in cattle keeping communities. The gendered induced vulnerabilities related to the socio-cultural norms and familial roles, also play an important role in the exposure and spill over at the individual, interpersonal and community levels. The insufficient knowledge-sharing and reluctance to adopt preventive measures emerge as structural contributors to the persistence of brucellosis and other emerging zoonoses. These factors, intertwined with family dynamics and power relations, call for targeted interventions that address both individual behaviors and broader socio-cultural and institutional barriers to effective disease management and prevention. Conversely, policies that align with the community’s social construction, gender and context are more likely to be feasible, adopted and sustained by the affected population.

Theoretical modeling of 2,4-dichlorophenoxyacetic acid on acid-treated peanut skin: microscopic analysis via statistical physics treatment

Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analyses

Despite the observed benefits of properly prescribed exercises for people with Amyotrophic Lateral Sclerosis (ALS), the scarcity of studies and lack of consensus on the effects of muscle-strengthening exercises on this population has a negative impact on their rehabilitation. This study aimed to evaluate the effects of muscle-strengthening interventions in individuals with ALS. This systematic review of intervention studies included clinical trials that performed non-respiratory muscle strengthening in people with ALS compared to non-strengthening interventions, usual care, or placebo. Such studies were obtained from the MEDLINE, EMBASE, Cochrane Library, SPORTDiscus, and Physiotherapy Evidence Database databases, with no language or publication date restrictions. The outcomes considered were peripheral muscle strength, functionality, fatigue, and adverse events. The Physiotherapy Evidence Database scale was used to analyze the risk of bias, while the Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the quality of the evidence. Searches were conducted in October 2023 and eight studies were included, totaling 296 individuals. Seven of the eight studies showed superiority of the experimental intervention over the control, but this was not supported in the meta-analyses. Small sample size and high heterogeneity in the primary studies contributed significantly to the low quality of the evidence. There was no evidence of the superiority of interventions for muscle strengthening compared to interventions not aimed at strengthening, usual care, or placebo in terms of the outcomes analyzed immediately after the intervention. The quality of the evidence ranged from low to very low. Five of the studies evaluated adverse events, without reporting serious events. Interventions for muscle strengthening did not prove to be more effective when compared to the control group in the short term nor seem to produce serious adverse events. The low quality of the evidence indicates the need for studies with greater methodological rigor in this population, to more assertively assess the impacts of this intervention over the short, medium, and long term.

Gradient in grammatical structure of indigenous languages reflects pathway of human expansion in the Americas

Abstract The settlement of the Americas is one of the major episodes of prehistoric human dispersal, and involved multiple temporally and geographically uneven demographic events that continued into the Holocene. Here we suggest the possibility that these complex dynamics are reflected in the spatial structure of Indigenous linguistic diversity. On the basis of newly collated data, we find more pronounced spatial structure in linguistic diversity in North America than in South America after known genealogy and language contact are accounted for. Furthermore, we report a continent-wide gradient in aspects of sound systems and grammatical structure that mirrors early north–south dispersal paths, and that is not explained by local language contact and known phylogenetic relationships.

COVID-19 pandemic and risk factor measurement in individuals with cardio-renal-metabolic diseases: A retrospective study in the United Kingdom

Background Comprehensive research about changes in risk factor (RF) management of people with chronic conditions during the COVID-19 pandemic is sparse. We aimed to study the impact of the pandemic on RF assessment in people with type 2 diabetes (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD). Method Using UK Clinical Practice Research Datalink GOLD, we identified adults with T2DM, CVD and CKD who were alive and registered two years before (March 2018 – February 2019; March 2019 – February 2020) and one year during (March 2020 – February 2021) the pandemic. We estimated the proportion of people whose RFs (systolic (SBP) and diastolic (DBP) blood pressure, total cholesterol (TC), body mass index, smoking, and HbA1c) were assessed, mean values, and the proportion of controlled at each period for each cohort, overall and by age, sex, ethnicity, and deprivation. Multivariable logistic regression was used to estimate the association of patient characteristics (age, sex, ethnicity, deprivation, and comorbidity) with the outcome of having all RFs assessed during a given period. Results Within the T2DM cohort, 66.4% and 65.2% had assessments of HbA1c in 2018 and 2019, which reduced to 43.4% in 2020. In CVD cohort, 76.9% and 72.6% had their BP measurements (54.5% and 51.3% for TC) in 2018 and 2019 respectively, which declined to 40.6% (30.7% for TC) in 2020. In CKD cohort, BP assessments declined from 77.9% and 72.3% in 2018 and 2019 respectively to 45.0% in 2020. These findings were consistent across patient demographics. In those with T2DM, SBP and DBP increased (+1.65 mmHg and +1.02 mmHg) in 2020. Elderly people were less likely to have all their RFs assessed in 2020 in all three cohorts compared to previous years. Conclusions Among people with major cardiometabolic conditions, there have been substantial reductions in the assessment and control of several key RFs during the pandemic. These patients will need regular monitoring in future for the prevention of complications. Our findings also highlight the need for resilient healthcare systems to ensure continuity of care and mitigate disparities in high-risk populations.

Integrating bioinformatics and machine learning to discover sumoylation associated signatures in sepsis

Abstract Small Ubiquitin-like MOdifier-mediated modification (SUMOylation) is associated with sepsis; however, its molecular mechanism remains unclear. Herein, hub genes and regulatory mechanisms in sepsis was investigated. The GSE65682 and GSE95233 datasets were extracted from public databases. Differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted in GSE65682 to identify differentially expressed genes (DEGs) and key module genes. Candidate genes were derived by intersecting with SUMOylation-related genes (SUMO-RGs). The Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) were utilized to identify significant feature genes. The convergence of those genes was utilized for diagnostic assessment and expression validation. Hub genes were defined as those exhibiting an area under the curve (AUC) greater than 0.7, significant gene expression, and a consistent trend. Localization and functional analyses of hub genes were conducted to enhance the understanding of these genes. Immune analysis, regulatory network construction, and drug prediction were performed. Six hub genes were identified: RORA, L3MBTL2, PHC1, RPA1, CHD3, and RANGAP1. These genes possessed considerable diagnostic significance for sepsis and were also markedly downregulated in the condition. Hub genes were predominantly enriched in the ribosome pathway and exhibited a strong correlation with differential immune cells. Activated CD8 + T cells exhibited a positive correlation with RORA. Based on the predicted and established regulatory network, AC004687.1 was observed to modulate PHC1 expression via hsa-miR- 142 - 5p. A total of six hub genes (RORA, L3MBTL2, PHC1, RPA1, CHD3, and RANGAP1) associated with SUMOylation was identified in sepsis in the current study. The findings are likely to aid in the differentiation between control and disease states, offering substantiation for the diagnosis of sepsis.

Temporal changes in cecal luminal and mucosal microbiota of broiler chickens with clinical coccidiosis (Eimeria maxima)

Coccidiosis is a gastrointestinal disease caused by Eimeria parasites which leads to major economic losses in the poultry industry worldwide. Eimeria infection may alter the gut microbiota, which has been associated with chicken health and performance. This study aimed to determine the effects of Eimeria maxima infection on the luminal and mucosal microbiota of the cecum (CeL and CeM) at multiple time points post-infection (days 3, 5, 7, 10, and 14). Infection decreased Shannon diversity at d 3 (P = 0.03), increased observed features (ASVs) at d 5 (P < 0.01), and increased Shannon diversity at d 10 (P = 0.04) in the CeL microbiota compared to the control. In CeM microbiota, infection increased observed features at d 5 (P = 0.03), but later decreased observed features at d 14 (P = 0.01). Relative abundance of potential butyrate-producing bacteria such as [Ruminococcus] torques group in CeL and Butyricicoccus in CeM were decreased in infected birds, and some metabolic pathways related to butyrate production were predicted to be decreased. These findings show E. maxima may affect cecal microbiota alpha diversity in a time-dependent manner and reduce abundance of bacteria potentially important to gut health.

Mechanism and role of H. pylori CagA-induced NLRP3 inflammasome in gastric cancer immune cell infiltration

Genetic diversity and demographic history of the largest remaining migratory population of brindled wildebeest (Connochaetes taurinus taurinus) in southern Africa

The blue wildebeest (Connochaetes taurinus) is a keystone species in the savannahs of southern Africa, where it maintains shortgrass plains and serves as an important prey source for large carnivores. Despite being the second-largest migratory wildebeest population, the brindled wildebeest (C. t. taurinus) of the Greater Liuwa Ecosystem (GLE) of western Zambia have remained largely unstudied, until recently. While studies have increased understanding of recent demography, migration, and population limiting factors, the level of genetic diversity, patterns of gene flow, and long-term demographic history of brindled wildebeest in the GLE remains unknown. Most genetic studies of wildebeest have focused on small, heavily-managed populations, rather than large, migratory populations of high conservation significance. We used restriction-site associated DNA sequencing (RAD-seq) to assess genetic diversity, population structure, and demographic history of brindled wildebeest in the GLE. Using SNPs from 1,730 loci genotyped across 75 individuals, we found moderate levels of genetic diversity in GLE brindled wildebeest (He =  0.210), very low levels of inbreeding (FIS =  0.033), and an effective population size of about one tenth the estimated population size. No genetic population structure was evident within the GLE. Analyses of the site frequency spectrum found signatures of expansion during the Middle Pleistocene followed by population decline in the Late Pleistocene and early Holocene, a pattern previously observed in other African ungulates. These results will supplement field studies in developing effective conservation plans for wildebeest as they face continued and increasing threats of habitat loss, poaching, and other human impacts across their remaining range.

Leveraging TME features and multi-omics data with an advanced deep learning framework for improved Cancer survival prediction

Study protocol for a randomized single-center cross-over study: Dapagliflozin treatment in recurring kidney stone patients

Introduction Urolithiasis is one of the most common diseases worldwide, characterized by high morbidity and significant treatment-related costs, with a rising prevalence of up to 20%. The relapse rate within the first 10 years after initial treatment is estimated to be about 60%. Given the increasing prevalence, healthcare-related costs associated with urinary tract stones in the USA are expected to reach up to US $1.24 billion annually by 2030. Current prophylactic therapy for urolithiasis recurrence includes lifestyle modifications, citrate supplementation, and pharmaceuticals. However, a high number of cases remain unresponsive to available pharmacological therapies. Though initially developed for the treatment of Diabetes mellitus, SGLT-2 inhibitors have shown promise in decreasing cardiac and renal endpoints across multiple indications. Recent registry studies have indicated that patients receiving SGLT-2 inhibitors exhibit lower rates of urolithiasis incidence, suggesting a potential reduction in recurrence rates and associated mortality. Objectives We hypothesize that SGLT-2 inhibitors (Dapagliflozin), owing to their multiple pleiotropic effects, may offer a viable treatment option for the prophylaxis of high-risk calcium oxalate kidney stones and reduce urinary calcium oxalate output. Methods This study will proceed in two phases: an exploratory phase and a randomized controlled phase. In the exploratory phase, 22 participants with indications for dapagliflozin treatment will be evaluated before and after treatment initiation to ascertain the concrete effect size regarding oxalate and calcium-sparing effects. This data will inform the calculation of the study sample size (ranging from 17 to 104 participants) to include high-risk calcium oxalate kidney stone formers in a randomized controlled crossover study design. Treatment phases—one with dapagliflozin and one with placebo—will alternate with wash-out phases involving placebo. The primary outcome is the reduction of oxalate excretion in 24-hour urine samples compared to baseline values after 8 weeks of therapy. Secondary objectives include analysing effects on kidney function, the frequency of urolithiasis, and treatment tolerance. Additionally, in-depth metabolomics analyses will explore pathophysiological pathways during treatment. Investigators, patients, and research staff will be blinded to the randomization list. This study was initially registered under EudraCT (Nr:2022-000994-13) and has been transitioned to CTIS (Nr: 2024-519371-25-00) to comply with EU Regulation 536/2014, ensuring streamlined management and transparency. Discussion Dapagliflozin’s pleiotropic effects may provide a novel prophylactic treatment option for urolithiasis. This study aims to evaluate potential treatment effects in a prospective RCT and elucidate potential pathophysiological pathways through in-depth metabolomics analyses. SGLT-2 inhibitors have the potential to transform the landscape of urolithiasis treatment, reduce the healthcare burden on individuals and the system, and significantly improve patient quality of life.

The efficacy of the theory of planned behaviour and value-belief-norm theory for predicting young Chinese intention to choose green hotels

Abstract Although hotels have begun to pay more attention to green practices in providing products and services to satisfy guests’ green needs, the percentage of guests visiting green hotels is still low. Researchers undervalue the connection between consumers’ values, attitudes, norms, and intentions to stay at green hotels. Recently, scholars suggested that the attitude-intention gap can be closed by combining the theory of planned behaviour and the value-belief-norm theory. Therefore, this study examined the interrelationships among various constructs based on both theories. A total of 406 university students from Xuzhou City, China were employed quantitatively, utilising a purposive sample technique to test hypotheses using the Statistical Package for the Social Sciences and structural equation modelling. The results demonstrated that altruistic value, biospheric value, and collectivistic value positively influenced ecocentric attitude respectively. Implicit attitude was positively influenced by biospheric value, collectivistic value, and ecocentric attitude. Meanwhile, ecocentric attitude positively influenced awareness of consequence, subsequently ascription of responsibility, then the personal norm, and finally intention. Furthermore, implicit attitude, subjective norm, and perceived behavioural control positively influenced intention separately while subjective norm favourably influenced implicit attitude, perceived behavioural control, and personal norm respectively. The findings of this study would significantly contribute to a deeper understanding of consumers’ green hotel visits based on a combined theoretical framework from a developing country with a highly collectivistic value orientation, which benefits the growth of the green hotel industry and other key stakeholders.