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Abstract Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.7–NR, median follow-up 50 months). The secondary endpoint, biochemical PFS, was 48.6 months (95% CI: 39.9–NR) and coincided with or preceded SLiM-CRAB in eight patients. For additional secondary objectives, the overall response rate was 93% with 31% achieving complete response (CR) and 45% very good partial response (VGPR) or better. CR correlated strongly with the absence of SLiM-CRAB and biochemical progression. MRD-negativity (10-5 sensitivity) predicted a 5-year biochemical PFS of 100% versus 40% in MRD-positive patients (p = 0.051), demonstrating that deep responses significantly improve time to progression. Exploratory single-cell RNA sequencing linked tumor MHC class I expression to proteasome inhibitor response, and a lower proportion of GZMB+ T cells within clonally expanded CD8+ T cells associated with suboptimal outcomes.

Abstract This review synthesizes 48 academic studies on Initial Coin Offerings (ICOs) from 2018 to 2023, employing bibliometric and content analyses to illuminate their complexities and innovation in entrepreneurial finance. It identifies four key themes: (1) regulatory intricacies, market transformation, and strategic implications for emerging ventures; (2) the opportunities and challenges presented, and key factors influencing the success of ICOs; (3) ICOs and entrepreneurial finance; and finally, (4) review of reviews. By examining the intersection of legal frameworks, disruptive potential, and stakeholder challenges, this interdisciplinary perspective captures the essence of ICOs and charts a course for future inquiry. It serves as a pivotal reference for researchers, practitioners, and regulators to understand the multifaceted ICO landscape and its implications for the future of finance.

Abstract Background: In patients with eosinophilic esophagitis (EoE), the correlation between symptoms of esophageal dysfunction and endoscopic and histologic disease activity is generally poor and probably related to multiple causes such as esophageal remodeling processes that might go undetected using endoscopy and histology as well as esophageal hypervigilance and symptom-specific anxiety. Hence, there is a need for a holistic management of patients that goes beyond the control of eosinophilia and symptoms. Summary & Key messages: Physiological esophageal testing using high-resolution manometry, functional lumen imaging probe, pH-impedance, wireless pH monitoring and mucosal impedance may unveil the effects of chronic transmural fibro-inflammatory changes of the esophageal wall as well as esophageal hypervigilance, thereby assisting to phenotype patients, predict therapeutic response to therapy and identify motility disorders that may need a specific targeted therapy to ameliorate patients’ outcomes. This article discusses the role of functional esophageal examinations in the diagnosis and management of EoE.

Abstract The continuous growth of biofilm infections and their resilience to conventional cleaning methods and antimicrobial agents pose a worldwide challenge across diverse sectors. This persistent medical, industrial, and environmental issue contributes to treatment challenges and chronic diseases. Lactic acid bacteria have garnered global attention for their substantial antimicrobial effects against pathogens and established beneficial roles. Notably, their biofilms are also predicted to show a promising control strategy against pathogenic biofilm formation. The prevalence of biofilm-related problems underscores the need for extensive research and innovative solutions to tackle this global challenge. This novel study investigates the effect of different extracts (external, internal, and mixed extracts) obtained from Lactobacillus rhamnosus GG biofilm on pathogenic-formed biofilms. Subsequently, external extracts presented an important eradication effectiveness. Furthermore, a 6-fold concentration of these extracts led to eradication percentages of 57%, 67%, and 76% for Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa biofilms, respectively, and around 99.9% bactericidal effect of biofilm cells was observed for the three strains. The results of this research could mark a significant breakthrough in the field of anti-biofilm and antimicrobial strategies. Further studies and molecular research will be necessary to detect the molecules secreted by the biofilm, and their mechanisms of action engaged in new anti-biofilm strategies.

Abstract Background Disparities in health outcomes among persons with disabilities (PWD) are influenced by preventable factors including negative attitudes and discriminatory practices of healthcare professionals and the limited training of medical students in working with PWD. Objective The purpose of this study was to validate the “Medical Students’ Attitudes Towards Patients with Disabilities” (MSA-PWD) scale among Lebanese medical students and identify associated factors. Method A scale validation study was conducted as part of the standard internal evaluation process at the medical school, using a cross-sectional design based on a qualitative content validity process, involving students from years 1 to 4. The study included questions from previous tools, and others encouraging students to reflect on their encounters with PWD and share their insights. Statistical procedures were applied to assess the reliability and validity of the tool, including construct validity, convergent validity, known-group validity, and trend analysis. Results After a careful selection of the related items, the MSA-PWD scale demonstrated high construct validity and internal consistency, along with good convergent validity and known-group validity. Factor 1 of the scale was able to differentiate between different enrollment years of medical students, correlating with the self-assessment tool for confidence in dealing with PWD and clinical experience scenarios. Conclusion The “Medical Students’ Attitudes Towards Patients with Disabilities” scale validated in this study is a comprehensive instrument that can distinguish between different medical school enrollment classes. The newly developed scale was valid, and reliable.

Abstract Background Diabetes is associated with impairments in muscle mass and quality increasing the risk of sarcopenia. Thus, this study aimed to investigate the odds of sarcopenia and its associated risk factors among Qatari adults (> 18 years), while exploring the modulating effects of health and lifestyle factors. Methods Using a case–control design, data from 767 participants (481 cases with diabetes and 286 controls without diabetes) was collected from Qatar Biobank (QBB). Sociodemographic, lifestyle factors including dietary intake, anthropometric and biochemical measures were analyzed. Handgrip strength, Dual X-ray absorptiometry (DXA), and Bio-impedance were used to assess muscle strength, muscle mass and muscle quality, respectively. The risk of sarcopenia was estimated using the European consensus on definition and diagnosis of sarcopenia. Results Cases with diabetes were older (55 vs. 36 years; P

This paper investigates the potential that mediated text can have on expanding Lebanese young people's notions and understandings of sexuality beyond their personal boundaries and the immediate local context to uncover the portrayal of these notions within a global mediated space. It specifically seeks to examine the intersection between Lebanese youth media practices and sexual learning by identifying the extent to which watching the hit Netflix series "Sex Education," affected young people's sexual identities, knowledge and practices. Four focus groups, each comprised of six respondents, described the importance of the series in influencing young people's sexual learning and thoughts in a society where sexuality and sexual subjects are taboo. The four main discussion themes that were developed -- namely, Open Mindedness: transgression, acceptance and respect; Transformation: life skills and right choices; Gender Equality, Well-being and Health; Reliability/identification and the Need for Trustworthy Connections; and the Need to Re-educate Family and Society about Sex -- underscore the importance of the series as a learning tool, the need for the re-introduction of sexual education as part of school curricula in Lebanon, and the re-education of society more generally to help foster healthier sexual lives among young people.

Many mothers do not communicate with their adolescent about sexual health topics due to perceived barriers. Our goal in this study was to shed light on the activities mothers engage in to prepare for sexual health discussions with their young adolescents. We also examined the extent to which mothers' past sexual communication behaviour and intentions were associated with engaging in these activities and perceptions of their helpfulness. Participants were 244 mothers of young adolescents who completed surveys at two points in time separated by 6 months. Overall, 64% of the mothers had engaged in one or more preparatory activity but found doing so only somewhat helpful. More extensive past sexual communication and higher sexual communication intentions were associated with engaging in preparation activities and finding them more helpful. However, past communication was significantly associated with the likelihood of engaging in preparatory behaviours for mothers with low, average, but not high sexual communication intentions. The results point to the importance of strengthening mothers' sexual communication intentions and providing them with information about high-quality resources and/or a resource package as means to increase the likelihood that they will engage in activities that prepare them to discuss sexual health topics with their adolescent.

Background: The Food and Drug Administration (FDA) in the US approved primary human papillomavirus (HPV) testing for speculum-based cervical cancer screening ten years ago and, in May 2024, approved the self-collection technique. Our study defines the kappa agreement between self- and speculum-based collection techniques for 15 types of high-risk HPV. Additionally, we describe the sensitivity and specificity ratios for HPV testing using both collection methods. Methods: Participants recruited in 2020–2022 included 97 colposcopy attendees and 96 routine primary care screening attendees aged 30–65, who agreed to self-sample before their clinically scheduled speculum-based exam. Prevalence-based kappa calculated agreement, sensitivity and specificity ratios calculated accuracy using the cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) threshold. Results: The average ages were 45.9 (SD 10.5) and 46.2 (SD 11.0) years for the colposcopy and primary care attendees, respectively. HPV 16, 68, and 39 were the most common types detected. The lower bound of the 95 % Cl for kappa calculations was above 0.81, indicating almost perfect agreement across all HPV genotypes. The sensitivity and specificity ratios were consistent at 1.0 across both collection methods. The HPV positivity rate was significantly higher among colposcopy attendees at 66 % (64/97), compared to 14 % (13/96) among routine primary care screeners. The study identified 17 women with CIN2 + . Conclusions: Primary HPV screening with self-collection is equivalent to speculum-based collection among people aged 30–65. The findings emphasize the utility of self-collection in identifying high-grade lesions and the consistency of HPV detection across different collection methods.

Infant formula milk (IFM) is increasingly utilized as a substitute for natural breastfeeding despite the fact that breast milk has been always recognized as the optimal nourishment method. While IFMs are fortified with essential nutrients that are crucial for proper growth, they can also harbor non-essential toxic metal contaminants from various sources during the production process. Given the heightened vulnerability of newborns to such contaminants, it is imperative to thoroughly analyze, evaluate, and minimize the toxicity associated with the consumption of such IFMs. However, classical approaches to date, have been always adopted for assessing such risks by finding first the analytical concentration of metals in the IFMs followed by multiplying it by the average daily powder intake (ADI) then dividing by the average infant weight. The outcome is then compared to an established standard such a PTWI to assess the extent of toxicity. The drawback with such studies is the use of a fixed ADI for all samples as if all samples have the same and exact preparation directions while using somewhat different infant masses.Accordingly, this study aims at assessing the toxic risk amongst newborns from IFM consumption through the identification and application of various highly important and toxicity-contributing parameters from each IFM and its directions of preparation label separately which are discussed here for the first time while providing comparisons between the classical approach versus our new approach to highlight its importance.Seventy-three IFMs (0–6 months) were analyzed for lead (Pb), cadmium (Cd), arsenic (As), and aluminum (Al) levels and unlike previous studies, this work incorporated various feeding parameters from each IFM for calculating the intakes thus, revealing potential toxicity risks even in IFMs that are considered safe by the classical approach. Metal contamination was significant, with 97.3 % of samples containing detectable Pb, 41.1 % Cd, 16.4 % As, and 93.2 % Al while highlighting Pb in exceeding its maximum allowable level (MAL). This novel approach, which considers new diverse feeding schedules/parameters that are ironically suggested by manufacturers that have been previously overlooked elsewhere, emphasized IFMs' potential as sources of heightened metal toxicity in comparison to classical approaches. Results highlighted Pb and Al as major concerns, with As and Cd of lesser concern. Findings also emphasized the importance of such new parameters for safeguarding newborn health and should be payed attention to by caregivers. The study strongly and highly recommends adherence to minimum feeding schedules (MFS) and proper scooping techniques to reduce newborn exposure to toxic metals. It also suggests continuous monitoring and stricter regulations by health authorities at the production level of such products so as to provide a safer commodity in the first degree and to also provide better and somewhat uniform and specific feeding labels and precautions on such products.

Background Urinary tract infections (UTIs) are among the most common bacterial infections, and appropriate antimicrobial therapy with agents that minimise resistance is crucial. Despite international concern, adherence to guidelines is still suboptimal. This study aims to determine the effect of the absence of national guidelines and the rate of conformity to international guidelines among physicians in antibiotic (ATB) prescriptions for the treatment of UTIs in adults and detect the factors that are associated with a higher rate of non-compliance.Methods Patient-related characteristics and the prescribed ATBs were gathered from patients' medical files, and a questionnaire was directed to physicians to elicit the factors involved in decision-making. Four criteria were evaluated: molecule conformity, daily dose conformity, duration conformity and global conformity.Results 37 Lebanese physicians and 185 prescriptions were included. The most prevalent class of ATBs was fluoroquinolones (30.3%). Global conformity to guidelines was 31.4%, while conformity on drug choice, daily dose and duration of treatment was 83.2%, 74.7% and 41.6%, respectively. There were no differences in conformity rates according to the physician’s specialty (p=0.135). Physicians who studied in an American-system university had an increased risk of non-conformity (adjusted OR (aOR=2.107, p=0.018). Patients with higher education levels, or presenting with fever or chills, were more likely to get a non-compliant prescription (aOR=2.140, p=0.032 and aOR=4.947, p=0.033, respectively).Conclusion In a country with no local guidelines, non-conformity to international guidelines is high. Larger national studies are needed with immediate interventions to enhance physicians’ prescribing practices. After local guidelines were established, it would be interesting to compare the rate of adherence to these guidelines.

This research explores the interdependence within the international logistics sector among 17 nations, utilizing a quantile-based technique to assess the transmission of returns. By analyzing daily data from DataStream spanning from 1 June 2016, to 12 August 2024, we apply the Quantile Vector Autoregression framework to examine the synchronous behavior of variables, considering the magnitude of shocks. Our findings reveal varying degrees of linkage at the lower, median, and upper quantiles of the conditional distribution. The results show that extreme events, such as the COVID-19 pandemic and the Russia-Ukraine war, significantly amplified spillovers across logistics markets, while the impact of the Israel-Hamas conflict was more regionally contained. Regional clustering and geographical proximity play a crucial role, with stronger interconnections observed among neighboring countries, such as the US and Canada, and Germany and France. The US stands out as a dominant transmitter of shocks, while countries in Asia and Oceania tend to be net receivers, highlighting their vulnerability to external disruptions. These results underscore the need for quantile-based risk assessments in regulatory frameworks and risk management strategies to better manage asymmetric risk transmissions during global crises.

This study investigates the changes and persistence in dynamic connectedness between stock market performance and exchange rate fluctuations, comparing conventional and Islamic financial systems. With an eye on a global financial landscape characterized by the integration of capital markets and the adoption of floating exchange rate regimes, it examines the effects of exchange rate variations on the dynamics of the stock market in nine different countries - the United Kingdom, Australia, Japan, Singapore, Canada, China, India, Korea, and South Africa. The study employs daily data spanning from November 2015 to July 2023 and uses a comprehensive analysis of three-step methodology, including nonparametric causality-in-quantiles tests, asymmetric slope Conditional Autoregressive Value-at-Risk (CAViaR), and Time-Varying Parameter Vector Autoregressive (TVP-VAR) Connectedness measure. Our results underline the asymmetric impact of exchange rate fluctuations on stock markets and highlights the distinctive characteristics of Islamic financial markets. Comparing Islamic and conventional stock markets in the context of exchange rate fluctuations, this study not only serves to fill a gap in the existing literature but also emphasizes the significance of currency exchange rate swings for global investors, policymakers, and practitioners trying to understand the intricacies of global financial markets.

Introduction: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. Methods: The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12–18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. Results: As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. Conclusion: SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.

Objective: The role of selective decontamination with oral antibiotics (OABs) and mechanical bowel preparation (MBP) prior to elective colorectal surgery is still widely debated. The objective of this study was to compare the outcomes of selective decontamination with neomycin, metronidazole and MBP compared to those of decontamination with MBP alone or with no preparation. Methods: Selective decontamination with neomycin and metronidazole combined with bowel preparation was introduced prior to elective colorectal surgery as part of an enhanced recovery after surgery program at Westmead Hospital, a major Australian tertiary referral hospital, between June 2017 and January 2023. Comparisons between short-term outcomes of OAB + MBP and MBP/no preparation were made using prospectively collected data on length of stay (LOS), readmission, mortality within 30 days, anastomotic leakage (AL), surgical site infection (SSI), urinary tract infection, deep venous thrombosis and/or pulmonary embolism, pneumonia, and ileus. Follow-up was limited to hospital stays and subsequent presentations within the health district within thirty days of surgery. The Mann–Whitney U test was used to analyse continuous data, and the chi-square test was used for categorical data. Univariate and multivariate regression modelling was performed to identify risk factors associated with an increased likelihood of SSI and AL. Results: Patients with oral neomycin and metronidazole combined with bowel preparation had reduced superficial SSI (2.7% vs. 7.6%, p = 0.043) and overall complications (32.7% vs. 44.6%, p = 0.020), particularly Clavien–Dindo 1 complications (7.3% vs. 16.5%, p = 0.009). However, the differences in AL (2.7% vs. 4.5%, p = 0.369) and organ/space SSI (1.3% vs. 3.7%, p = 0.327) were not statistically significant. The median LOS (6 d vs. 6 d, p = 0.370) was not different between the groups. Conclusion: Selective decontamination with neomycin and metronidazole reduces the risk of SSIs and overall complications. There was a trend to toward a lower AL, but this difference was not statistically significant.

This paper explores spatial systems of modularity on the shoreline of Ein el Mrayseh located in Beirut. The modular systems are studied from a contextual lens while observing different modular interventions as design strategies on this shoreline. The Ein el Mrayseh corniche is one of the few remaining public spaces of Beirut, and is considered one of the most important outlet for the city residents. It is used by different types of groups, from different classes and backgrounds. Based on a series of observations, the paper analyses modular interventions by different stakeholders on this stretch. Two terms were coined: rigid and soft modularity, as linguistic and analytical modes to understand the spatial practices of Ein el Mrayseh. The paper argues that the users of this public space have developed soft modular strategies - dynamic and in constant flux, as a mean to tame the rigid modular strategies enforced on the site and to appropriate the space.

Public health authorities face the issue of optimal vaccine distribution during the spread of pandemics. In this paper, we study the optimal way to distribute a finite supply rate of COVID-19 doses between either the first or second doses for unvaccinated individuals and the third doses (booster shots) for fully vaccinated individuals. We introduce a novel compartmental model that accommodates the vaccinated populations. This Booster model is implemented to simulate two prototypes of populations: one with a highly infected and highly vaccinated proportion, and another with a lowly infected and lowly vaccinated percentage. We namely use sample data from Russia and Djibouti, respectively.Our findings show that around one quarter of the vaccines should be employed as booster shots and the rest as first and second doses to minimize the deaths for the first type of population. On the other hand, the second type of population can minimize their number of deaths by mainly focusing on administering the initial two doses, rather than giving any booster shots. The novel Booster model allows us to study the effect of the third dose on a community and provides a useful tool to draw public policies on the distribution of vaccines during pandemics.