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Wonnam Kim,1,* Yeon-Cheol Park,2,3,* Bonhyuk Goo,2 Jung-Hyun Kim,2 Dongwoo Nam,3,4 Eunseok Kim,5,6 Hyun-Jong Lee,7 Dong-Hyun Pyun,8,9 Hae Sun Suh,8– 10 Yoonsung Lee,11 Man S Kim,11 Byung-Kwan Seo,2,3 Yong-Hyeon Baek2,3 1Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 2Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 3Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 4Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 5Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 6Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 7Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 8Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea; 9Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul, Republic of Korea; 10College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; 11Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Yong-Hyeon Baek, Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea, Tel +82 2 440 6099, Fax +82 2 440 714, Email byhacu@khu.ac.krPurpose: Knee osteoarthritis (KOA) is one of the most prevalent degenerative joint diseases worldwide. The herbal decoction, Dokhwalgisaeng-tang (DHGST), has been commonly used in East Asia to treat osteoarthritis. However, there is insufficient evidence to draw clear conclusions concerning its effectiveness and safety for patients with KOA. We aim to determine the efficacy, safety, and economic feasibility of DHGST compared with Celecoxib, an oral COX-2 inhibitor, for patients with degenerative KOA.Trial Design and Methods: This multicenter, randomized, noninferiority trial, involving 160 participants who will be randomized using block randomization with 1:1 allocation, will compare DHGST and Celecoxib. The total trial period is 24 weeks after random allocation, comprising 12 weeks of treatment and 12 weeks of follow-up. Participants with KOA will be administered 200 mg of DHGST (treatment group) or Celecoxib capsules (control group) for 12 weeks. Efficacy and safety evaluations will be conducted at weeks 0, 4, 8, and 12, and 24. The primary outcome measurement is the Korean Western Ontario McMaster score at week 12. Changes in pain intensity using a 100 mm visual analog scale, changes in quality of life using a EuroQol 5-dimension 5-level self-report survey, and patient satisfaction will also be measured to evaluate effectiveness between the two groups. A trial-based economic feasibility evaluation will be conducted to analyze treatment cost-effectiveness from societal and healthcare system perspectives. Drug safety will be assessed through adverse reactions and laboratory test findings.Discussion: This trial protocol has the following limitations. Applying a double-dummy design is not possible, as the tablet and granule forms can easily be distinguished visually, and achieving participant blinding is challenging. The trial findings are intended to inform participants, physicians, and other stakeholders in determining whether DHGST could be used as an alternative therapeutic option for KOA.Trial Registration Number: KCT0008424 (Clinical Research Information Service of the Republic of Korea), registered on 12 May 2023.Keywords: degenerative joint disease, Dokhwalgisaeng-tang, noninferiority trial, randomized controlled trial

Abstract MYCN-amplified RB1 wild-type (MYCN amp RB1 +/+) retinoblastoma is a rare and aggressive subtype, often resistant to standard therapies. Identifying unique MRI features is crucial for diagnosing this subtype, as biopsy is not recommended. This study aimed to differentiate MYCN amp RB1 +/+ from the most prevalent RB1 -/- retinoblastoma using pretreatment MRI and radiomics. Ninety-eight unilateral retinoblastoma patients (19 MYCN cases and 79 matched controls) were included. Tumors on T2-weighted MR images were manually delineated and validated by experienced radiologists. Radiomics analysis extracted 120 features per tumor. Several combinations of feature selection methods, oversampling techniques and machine learning (ML) classifiers were evaluated in a repeated fivefold cross-validation machine learning pipeline to yield the best-performing prediction model for MYCN. The best model used univariate feature selection, data oversampling (duplicating MYCN cases), and logistic regression classifier, achieving a mean AUC of 0.78 (SD 0.12). SHAP analysis highlighted lower sphericity, higher flatness, and greater gray-level heterogeneity as predictive for MYCN amp RB1 +/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCN amp RB1 +/+ and RB1 -/- retinoblastoma subtypes.

Hye Kyung Jin,1– 3 Eunyoung Kim1,3,4 1Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, South Korea; 2Department of Psychology, Seoul National University, Seoul, South Korea; 3Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, South Korea; 4Division of Licensing of Medicines and Regulatory Science, The Graduate School of Pharmaceutical Management, and Regulatory Science Policy, The Graduate School of Pharmaceutical Regulatory Sciences, Chung-Ang University, Seoul, South KoreaCorrespondence: Eunyoung Kim, Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, South Korea, Tel +82-2-820-5791, Fax +82-2-816-7338, Email eykimjcb777@cau.ac.krPurpose: Leadership is increasingly becoming a priority in the forms of higher education associated with the Fourth Industrial Revolution; however, few studies have examined it in the context of pharmacy education. This study investigated the levels of communication competence, critical thinking disposition, problem-solving ability, and leadership of pharmacy students, and identified factors related to leadership.Methods: This study was conducted using a nationwide cross-sectional online survey with a self-administered questionnaire. A total of 416 third-to-sixth-year pharmacy students from all 35 pharmacy schools in South Korea, completed the survey from September 1 to 15, 2019. Data were analyzed using descriptive statistics, t-tests, Pearson’s correlations, and multiple regression analysis. We verified construct validity by performing an exploratory factor analysis.Results: The pharmacy students revealed a moderate level of communication skills, critical thinking disposition, problem-solving ability, and leadership. Significant positive correlations were found among communication competence (r=0.724, p< 0.001), critical thinking disposition (r=0.615, p< 0.001), problem-solving ability (r=0.599, p< 0.001), and leadership. After adjustment for control variables, communication competence (β=0.319, p< 0.001) was found to be the most significant predictor of leadership (F=104.12, p< 0.001, R2=0.756).Conclusion: This study showed that the students’ leadership was influenced by their competence in communicating effectively, thinking critically, and solving problems. Pharmacy educators should acknowledge and implement innovative curriculum and assessment approaches in preparing pharmacy students for their professional paths.Keywords: leadership, communication competence, critical thinking disposition, problem-solving ability, pharmacy students

Glenn Yiu,1 Shilpa Gulati,2 Victoria Higgins,3 Emily Coak,3 Daniel Mascia,3 Eunice Kim,4 Galin Spicer,4 David Tabano4 1Department of Ophthalmology & Vision Science, University of California, Davis Health, Sacramento, CA, USA; 2New England Retina Consultants, Springfield, MA, USA; 3Adelphi Real World, Bollington, UK; 4Genentech, Inc., South San Francisco, CA, USACorrespondence: Glenn Yiu, Department of Ophthalmology & Vision Science, University of California, Davis Health, 4860 Y St, Sacramento, CA, 95817, USA, Tel +1 916 734 6602, Email gyiu@ucdavis.eduBackground: Anti-vascular endothelial growth factor (anti-VEGF) agents are widely prescribed for the treatment of neovascular age-related macular degeneration (nAMD). Although studies have investigated patient choice of anti-VEGF agent, little is known regarding factors that influence physician preference of anti-VEGF agent for their patients.Objective: To describe physician rationale and challenges in prescribing anti-VEGF treatments for patients with nAMD.Methods: Data were drawn from the Adelphi Real World nAMD Disease Specific Programme™, a cross-sectional survey with retrospective data capture of physicians and their patients with nAMD in the United States between October 2021 and May 2022. Physicians (n = 56) reported data for up to 13 consecutively consulting patients (n = 451), including current anti-VEGF treatments used, factors affecting physicians’ choice of anti-VEGF agent and treatment strategy, and restrictions on specific agents.Results: Most physicians prefer employing a “treat-and-extend” treatment strategy, over “fixed interval” or “pro re nata” strategies. However, in routine clinical practice, “treat-and-extend” was reported for less than half of nAMD-diagnosed eyes. Top factors influencing physician choice of anti-VEGF agent and treatment strategy included maximizing clinical benefit (eg visual acuity gains and fluid control), patient convenience, and reducing out-of-pocket costs. However, physicians also reported facing substantial roadblocks in prescribing their choice of anti-VEGF agent, including restrictions on approved agents and gaps in insurance coverage. Persistent fluid was the most common physician-selected reason for switching a patient away from an anti-VEGF agent.Conclusion: Physicians face barriers to prescribing their preferred anti-VEGF agents in real-world healthcare settings. Overcoming these challenges may improve treatment outcomes for patients with nAMD.Plain Language Summary: People with wet age-related macular degeneration (wet AMD) have problems with their eyesight that can lead to blindness if left untreated. Eye doctors (ophthalmologists) use a class of medicine called anti-VEGF agents to treat people with wet AMD. However, eye doctors often face challenges in prescribing their anti-VEGF agent of choice. We surveyed eye doctors to determine the reasons why they preferred some anti-VEGF agents over others, as well as the barriers to prescribing these anti-VEGF agents. Eye doctors reported that they usually choose a specific anti-VEGF agent because it leads to better vision, has lower cost for people with wet AMD, or may reduce the number of appointments needed for people with wet AMD. Eye doctors also noted that they face challenges in treating people with wet AMD, including restrictions and limited insurance coverage for certain anti-VEGF agents. Solving these problems could help eye doctors use their medicine of choice and improve eyesight even more when they treat people with wet AMD. Keywords: Macular degeneration, physicians, vascular endothelial growth factor, real-world clinical practice

Take-all disease, caused by the Ascomycete fungus Gaeumannomyces tritici, is one of the most important root diseases of wheat worldwide. The fungus invades the roots and destroys the vascular tissue, hindering the uptake of water and nutrients. Closely related non-pathogenic species in the Magnaporthaceae family, such as Gaeumannomyces hyphopodioides, occur naturally in arable and grassland soils and have previously been reported to reduce take-all disease in field studies. However, the mechanism of take-all protection has remained unknown. Here, we demonstrate that take-all control is achieved via local but not systemic host changes in response to prior G. hyphopodioides root colonisation. A time-course wheat RNA sequencing analysis revealed extensive transcriptional reprogramming in G. hyphopodioides–colonised tissues, characterised by a striking downregulation of key cell wall–related genes, including genes encoding cellulose synthases (CESA), and xyloglucan endotransglucosylase/hydrolases (XTH). In addition, we characterise the root infection biologies of G. tritici and G. hyphopodioides in wheat. We investigate the ultrastructure of previously described “subepidermal vesicles” (SEVs), dark swollen fungal cells produced in wheat roots by non-pathogenic G. hyphopodioides, but not by pathogenic G. tritici. We show that G. hyphopodioides SEVs share key characteristics of fungal resting structures, containing a greater number of putative lipid bodies and a significantly thickened cell wall compared to infection hyphae. We hypothesise that SEVs are fungal resting structures formed due to halted hyphal growth in the root cortex, perhaps as a stress response to locally induced wheat defence responses. In the absence of take-all resistant wheat cultivars or non-virulent G. tritici strains, studying closely related non-pathogenic G. hyphopodioides provides a much needed avenue to elucidate take-all resistance mechanisms in wheat.

Breeding programs around the world continually collect data on large numbers of individuals. To be able to combine data collected across regions, years, and experiments, research communities develop standard operating procedures for data collection and measurement. One such method is a crop ontology, or a standardized vocabulary for collecting data on commonly measured traits. The ontology is also computer readable to facilitate the use of data management systems such as databases. Blueberry breeders and researchers across the United States have come together to develop the first standardized crop ontology in blueberry (Vaccinium spp.). We provide an overview and report on the construction of the first blueberry crop ontology and the 178 traits and methods included within. Researchers of Vaccinium species—such as other blueberry species, cranberry, lingonberry, and bilberry—can use the described crop ontology to collect phenotypic data of greater quality and consistency, interoperability, and computer readability. Crop ontologies, as a shared data language, benefit the entire worldwide research community by enabling collaborative meta-analyses that can be used with genomic data for quantitative trait loci, genome-wide association studies, and genomic selection analysis.

Yoona Oh,1,2,&ast; Chang-Hyun Han,3,4,&ast; Yeonhak Kim,1 Jihun Kim,1 Changsop Yang,3 Young Eun Choi,5 Byoung-Kab Kang,3 Kun Hyung Kim,1,2 Gi Young Yang,1,2 Byung Ryul Lee,1,2 Eunseok Kim1,2 1Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 2Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 3KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 4Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 5Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Eunseok Kim, Division of Clinical Medicine, School of Korean Medicine, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam, 50612, Republic of Korea, Tel +82 55 360 5950, Fax +82 55 360 5890, Email eskim@pusan.ac.krPurpose: Pharmacopuncture therapy (PPT) combines medicinal extracts with acupuncture and is widely used as an adjunct in clinical practice. This study assessed the safety and feasibility of PPT in addition to conventional Korean Medicine treatment (CKMT), including electroacupuncture, cupping and infra-red, for lumbar spinal stenosis (LSS).Patients and Methods: Forty patients diagnosed with LSS were randomly assigned to undergo PPT with CKMT (experimental group) or CKMT alone (control group) at a 1:1 ratio, receiving 10 sessions of each intervention over five weeks. The primary clinical outcome was measured using the 100-mm Visual Analog Scale (VAS) for buttock and leg pain five weeks post-treatment. Secondary outcomes included clinically important difference (CID), Zurich Claudication Questionnaire, self-reported walking capacity, Modified–Modified Schober test, EuroQol 5-dimension 5-level questionnaire, and the patient’s global impression of change. The adverse events were assessed at each visit. The analysis of covariance was conducted to compare between two groups.Results: Intervention completion rates were 95% and 100% in the experimental and control groups, respectively. No statistically significant differences were found between groups regarding the primary outcome (adjusted mean difference: 8.0; 95% confidence interval: − 1.4– 17.4). The mean difference in the 100-mm VAS for low back pain at week 5 (adjusted mean difference: 12.9; 95% confidence interval: 2.4– 23.4) and the proportion of patients who reached the minimum CID was higher in the experimental group than in the control group. However, no significant differences were observed with other secondary outcomes. One patient in the experimental group experienced a systemic skin rash that resolved the same day, whereas the adverse events in the other group were mild and transient.Conclusion: This trial demonstrated the feasibility of add-on effects and the safety of pharmacopuncture in patients with LSS. Further studies are warranted to evaluate the add-on effects of PPT in treating LSS.Trial Registration: Clinical Research Information Service (CRIS), KCT0007229; registered on April 26, 2022.Keywords: lumbar spinal stenosis, pharmacopuncture therapy, add-on effect, conventional Korean medicine treatment, pragmatic randomized pilot trial

This study presents a conceptual design of an Internet of Things (IoT) communication system for monitoring power generation systems in Colombian Non-Interconnected Zones (NIZs), which lack IoT connectivity due to complex geographical factors. The proposed system aims to ensure the proper operation and energy efficiency of off-grid systems while tracking the variables that influence their performance.The methods used in this study include identifying the needs of such a system, identifying requirements, obtaining technical specifications, and developing a conceptual design. The study also analyses and compares various technologies, including Wi-Fi, Bluetooth, LoRa and ZigBee, to determine which ones are best suited for IoT system design.The conceptual design of the proposed IoT monitoring system considers the geographical, communication and coverage characteristics of the NIZs and the technical characteristics of the energy projects to provide a complete functional system that can connect approximately 2 million people located in these isolated and vulnerable zones. Finally, the defined system can serve as a precedent for building prototypes in various NIZs, and research on IoT technologies suitable for NIZs can help us seek the technologies that are most suitable for these areas. Depending on the application and conditions of the energy project, the most appropriate technology can be determined on a case-by-case basis.

Introduction: The mainstreaming of genomics across healthcare specialties necessitates that all nurses and midwives have a high literacy in genomics.Methods: We aimed to design, develop, implement and evaluate a genomics education workshop for nurses and midwives using action research principles.Results: Registered nurses and midwives completed an online survey regarding genomics confidence and learning needs (n = 274). The results of this survey were used to develop the genomics education workshop. The workshop was run three times (n = 105) with evaluation data being collected both before and after each workshop. Significant improvements in confidence across all learning domains was found following the workshops (p < 0.001). A desire for more education across all learning domains except for genetics knowledge was also identified (p < 0.001).Discussion: Genomics education workshops were found to increase the confidence of nurses and midwives across a range of specialties. Nurses and midwives also expressed a desire for further education in genomics.

Abstract Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.

Symptomatic aortic stenosis and frailty reduce health-related quality of life (HrQoL). Transcatheter aortic valve implantation (TAVI) in patients at high to extreme risk has been proven to have a beneficial effect on HrQoL. Currently, TAVI is also considered in patients at intermediate risk. Our meta-analysis investigates whether benefits to HrQoL after TAVI is more pronounced in frail patients and patients at high to extreme vs. intermediate surgical risk. A systematic search of the literature was performed in November 2021 and updated in November 2023 in PUBMED, EMBASE, and the Cochrane Controlled Trials Register. Statistical analysis was performed according to the inverse variance method and the random effects model. A total of 951 studies were assessed, of which 19 studies were included. Meta-analysis showed a mean increase in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score of 29.6 points (6.0, 33.1) in high to extreme risk patients versus 21.0 (20.9, 21.1) in intermediate risk patients (p < 0.00001) and 24.6 points (21.5, 27.8) in frail patients versus 26.8 (20.2, 33.4) in the general TAVI population (p = 0.55). However, qualitative analyses of non-randomized studies showed the opposite results. In conclusion, TAVI improves HrQoL more in high to extreme than intermediate risk patients. Frailty’s impact on HrQoL post-TAVI is inconclusive due to varying outcomes in RCTs vs. non-RCTs.

Abstract Conservation funding is currently limited; cost‐effective conservation solutions are essential. We suggest that the thousands of field stations worldwide can play key roles at the frontline of biodiversity conservation and have high intrinsic value. We assessed field stations’ conservation return on investment and explored the impact of COVID‐19. We surveyed leaders of field stations across tropical regions that host primate research; 157 field stations in 56 countries responded. Respondents reported improved habitat quality and reduced hunting rates at over 80% of field stations and lower operational costs per km2 than protected areas, yet half of those surveyed have less funding now than in 2019. Spatial analyses support field station presence as reducing deforestation. These “earth observatories” provide a high return on investment; we advocate for increased support of field station programs and for governments to support their vital conservation efforts by investing accordingly.

Abstract Background The presence of in-house attending trauma surgeons has improved efficiency of processes in the treatment of polytrauma patients. However, literature remains equivocal regarding the influence of the presence of in-house attendings on mortality. In our hospital there is a double trauma surgeon on-call system. In this system an in-house trauma surgeon is 24/7 backed up by a second trauma surgeon to assist with urgent surgery or multiple casualties. The aim of this study was to evaluate outcome in severely injured patients in this unique trauma system. Methods From 2014 to 2021, a prospective population-based cohort consisting of consecutive polytrauma patients aged ≥ 15 years requiring both urgent surgery (≤ 24h) and admission to Intensive Care Unit (ICU) was investigated. Demographics, treatment, outcome parameters and pre- and in-hospital transfer times were analyzed. Results Three hundred thirteen patients with a median age of 44 years (71% male), and median Injury Severity Score (ISS) of 33 were included. Mortality rate was 19% (68% due to traumatic brain injury). All patients stayed ≤ 32 min in ED before transport to either CT or OR. Fifty-one percent of patients who needed damage control surgery (DCS) had a more deranged physiology, needed more blood products, were more quickly in OR with shorter time in OR, than patients with early definitive care (EDC). There was no difference in mortality rate between DCS and EDC patients. Fifty-six percent of patients had surgery during off-hours. There was no difference in outcome between patients who had surgery during daytime and during off-hours. Death could possibly have been prevented in 1 exsanguinating patient (1.7%). Conclusion In this cohort of severely injured patients in need of urgent surgery and ICU support it was demonstrated that surgical decision making was swift and accurate with low preventable death rates. 24/7 Physical presence of a dedicated trauma team has likely contributed to these good outcomes.

Higher education institutions around the world were impacted by the COVID-19 pandemic that began in early 2020. Because U.S. community colleges focus on two-year degrees and workforce development, they were affected differently than their four-year counterparts. This study examined how academic administrators at different rural community colleges in Virginia, United States, perceived enrollment management practices that were implemented or changed due to the pandemic. This sequential explanatory study’s first phase was quantitative and measured mid- to senior-level administrators’ views of how the pandemic affected their colleges’ enrollment management practices. The second qualitative phase resulted in five themes surrounding COVID-related enrollment management practices: a) COVID-19 led to crisis management and operations in phases; b) managing student onboarding during COVID-19; c) COVID-19 created unique challenges for community college students; d) COVID-19 affected decision-making procedures; and e) COVID-19 resulted in work/life balance issues and COVID fatigue. Implications and future directions are provided to ensure that community college enrollment managers and policymakers understand how to continue to pivot to ensure student services are maintained or enhanced during a crisis.

Abstract The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignant Pax5 +/− B-cell precursors toward leukemia. Transcriptional profiling reveals that Myd88 is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction of Myd88 expression leads to a significant increase in leukemia incidence in Pax5 +/−Myd88+/− mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development in Pax5 +/− mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children.

Abstract Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains. Single-cell messenger RNA sequencing (scRNAseq) of Pf-infected HepOrg cells has identified 80 Pf-transcripts upregulated on day 5 post-infection. Transcriptional profile changes are found involving distinct metabolic pathways in hepatocytes with Scavenger Receptor B1 (SR-B1) transcripts highly upregulated. A novel functional involvement in schizont maturation is confirmed in fresh primary hepatocytes. Thus, HepOrgs provide a strong foundation for a versatile in vitro model for Pf liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control.

AbstractThe rapid depletion of fossil fuel reserves, population growth, and increasing environmental pollution have forced a change in the search for alternatives to produce and use energy. Currently, renewable energies (RE) have achieved more efficient advances to produce energy from non-conventional and inexhaustible sources, which can meet the basic needs of society and whose environmental impact is a door of opportunities for all. For this reason, academia has a preponderant role in ensuring that engineers are fully equipped with the necessary skills to provide feasible and contextualised solutions for this era of energy transition framed by the UN Sustainable Development Goals (SDGs). This article explores the impact on the development of the necessary skills for engineers in the renewable energy sector by tracing a route towards the acquisition of renewable energy knowledge with strategically organised work teams of undergraduate students, where two methodologies that are gaining ground in engineering education programs are applied: Problem Based Learning(PBL)and Design thinking (DT).After the validation of these techniques, it is concluded that bringing engineering students closer to real contexts related to renewable energies and above all with an objective of impact on communities, it is the right way to build knowledge in teams, in an immersive and committed way with the institution, which has developed and implemented an innovative pedagogical method based on the application of a critical educational model focused on the development of competencies, where the union of new technologies with the teaching processes on which this research is based is envisioned for the future.

Abstract Background Antibacterial resistance is a growing concern worldwide, including in Mozambique. Diarrhea is an important cause of mortality in Mozambique, yet few local studies have reported on the resistance of bacterial pathogens in this context. Therefore, this study aims to characterize antibiotic susceptibility patterns of Salmonella, Shigella and Campylobacter spp. among patients with diarrhea, including those who are HIV-infected and-uninfected. Methods We conducted antibiotic susceptibility testing on 157 stool isolates recovered from 129 patients aged between 0 and 80 years with diarrhea, including HIV infected (n = 68) and-uninfected individuals (n = 61), assisted at two health centers in Maputo city. The isolates comprised of 99 Salmonella, 45 Shigella and 13 Campylobacter strains. The Kirby-Bauer disk diffusion method was used on Mueller-Hinton II agar for Salmonella and Shigella spp., while Mueller-Hinton II agar with 5% defibrinated sheep blood was used for Campylobacter spp. We tested six antibiotics listed on the national essential medicines list, including ciprofloxacin, erythromycin, azithromycin, trimethoprim-sulfamethoxazole, gentamicin, and tetracycline. Results All isolates were resistant to at least one antibiotic. A high percentage of Salmonella spp. isolates were found to be resistant to trimethoprim-sulfamethoxazole (89.9%, n = 89), erythromycin (88.9%, n = 88) and tetracycline (76.8%, n = 76). In addition, 86.6% (n = 39) and 68.9% (n = 31) of Shigella isolates were resistant to trimethoprim-sulfamethoxazole and tetracycline, respectively. The majority of Campylobacter isolates (92.3%, n = 12) were resistant to erythromycin, azithromycin and tetracycline. Multidrug resistance (MDR) was observed in 79.8% of Salmonella spp., 76.9% of Campylobacter spp., and 57.8% of Shigella spp. Drug susceptibility profiles for Salmonella spp. and Campylobacter were similar in both HIV-1 infected and uninfected patients. However, Shigella spp. isolates obtained from patients without HIV infection were significantly more likely to be resistant to erythromycin, azithromycin or to exhibit multidrug resistance than those obtained from patients with HIV-1 infection (p

Hyun Chul Kim,1,2 Sangmi Lee,1,2 Siyoung Sung,3 Eunjin Kim,3 In-Jin Jang,1 Jae-Yong Chung4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea; 3Dong-A ST Research Institute, Yongin-si, Gyeonggi-do, Republic of Korea; 4Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of KoreaCorrespondence: Jae-Yong Chung, Seoul National University College of Medicine and Bundang Hospital, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea, Tel +82-31-787-3955, Fax +82-31-787-4045, Email jychung@snubh.orgBackground: Dapagliflozin formate (DAP-FOR, DA-2811), an ester prodrug of dapagliflozin, was developed to improve the stability and pharmaceutical manufacturing process of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor.Purpose: This study aimed to evaluate the pharmacokinetics (PKs) and safety of dapagliflozin for DAP-FOR compared to those for dapagliflozin propanediol monohydrate (DAP-PDH, Forxiga) in healthy subjects.Methods: This was an open-label, randomized, single-dose, two-period, two-sequence crossover study. The subjects received a single dose of DAP-FOR or DAP-PDH 10 mg in each period, with a 7-day washout. Serial blood samples for PK analysis were collected up to 48 hours after a single administration to determine plasma concentrations of DAP-FOR and dapagliflozin. PK parameters were calculated using a non-compartmental method and compared between the two drugs.Results: In total, 28 subjects completed the study. DAP-FOR plasma concentrations were not detected in all of the blood sampling time points except for one time point in one subject, and the corresponding DAP-FOR plasma concentration in the subject was close to the lower limit of quantification. The mean plasma concentration–time profiles of dapagliflozin were comparable between the two drugs. The geometric mean ratios and its 90% confidence intervals of the maximum plasma concentration and area under the plasma concentration–time curve of dapagliflozin for DAP-FOR to DAP-PDH were within the conventional bioequivalence range of 0.80– 1.25. Both drugs were well-tolerated, with a similar incidence of adverse drug reactions.Conclusion: The rapid conversion of DAP-FOR into dapagliflozin led to the extremely low exposure of DAP-FOR and comparable PK profiles of dapagliflozin between DAP-FOR and DAP-PDH. The safety profiles were also similar between the two drugs. These results suggest that DAP-FOR can be used as an alternative to DAP-PDH.Keywords: prodrugs, dapagliflozin, pharmacokinetics, clinical trial, phase I

Societal Impact statement To secure a stable, safe food supply, the future of humanity depends on the conservation and application of cultivated and wild plant diversity. Strawberries are globally important. They are widely produced and provide significant human health benefits. In 2019, annual world production was 14.5 MT (FAOSTAT, 2022). This report characterizes agricultural traits of diverse heritage strawberries. The gene pool of breeding programs has traditionally included a reliable but limited set of cultivars. The traits of lesser known heritage strawberry cultivars and selections examined by our study could be of value in expanding gene pools by tapping into existing cultivated genetic diversity. Summary Strawberries are a berry crop of global significance. We present a comprehensive evaluation of strawberry diversity through phenotyping 284 strawberry cultivars from the U.S. Department of Agriculture, National Clonal Germplasm Repository Corvallis, Oregon, USA. We assessed 284 cultivars in 2019 and 2020 for quantified variation across 16 traits, including phenology, plant morphology, and fruit quality traits at full ripeness. Through cluster analysis, we determined groups of accessions that had desirable traits, including quality fruits, earliest fruit ripening, or high numbers of daughter plant production. We observed that this strawberry diversity panel displayed a wide range of phenotypic variation that could prove useful for future strawberry improvement. ORUS 2427‐1, NW 90054‐37, and “Independence,” each developed by the Oregon USDA breeding program, displayed a combination of the highest fruit quality traits. “Independence” also had the longest runner length and the highest number of daughter plants. Two California cultivars, Oso Grande and Cuesta, and the Oregon cultivar Pinnacle had a short ripening time, on average 32 days between flowering and harvest, with the range for the study group of 25–41 days. Our data provide insight for breeders to expand gene pools, producers who choose cultivars for green‐wall production, or geneticists who need data to prepare genome‐wide association studies.

Replication Protein A (RPA) is single-strand DNA binding protein that plays a key role in the replication and repair of DNA. RPA is a heterotrimer made of 3 subunits – RPA1, RPA2, and RPA3. Germline pathogenic variants affecting RPA1 were recently described in patients with Telomere Biology Disorders (TBD), also known as dyskeratosis congenita or short telomere syndrome. Premature telomere shortening is a hallmark of TBD and results in bone marrow failure and predisposition to hematologic malignancies. Building on the finding that somatic mutations in RPA subunit genes occur in ~1% of cancers, we hypothesized that germline RPA alterations might be enriched in human cancers. Because germline RPA1 mutations are linked to early onset TBD with predisposition to myelodysplastic syndromes, we interrogated pediatric cancer cohorts to define the prevalence and spectrum of rare/novel and putative damaging germline RPA1, RPA2, and RPA3 variants. In this study of 5,993 children with cancer, 75 (1.25%) harbored heterozygous rare (non-cancer population allele frequency (AF) < 0.1%) variants in the RPA heterotrimer genes, of which 51 cases (0.85%) had ultra-rare (AF < 0.005%) or novel variants. Compared with Genome Aggregation Database (gnomAD) non-cancer controls, there was significant enrichment of ultra-rare and novel RPA1, but not RPA2 or RPA3, germline variants in our cohort (adjusted p-value < 0.05). Taken together, these findings suggest that germline putative damaging variants affecting RPA1 are found in excess in children with cancer, warranting further investigation into the functional role of these variants in oncogenesis.

Bonhyuk Goo,1,&ast; Yeon-Cheol Park,2,&ast; Eunseok Kim,3,4 Won-Suk Sung,5 Eun-Jung Kim,6 Jung-Hyun Kim,1 Byung-Kwan Seo,2 Yong-Hyeon Baek2 1Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 2Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 3Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 4Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan-si, Republic of Korea; 5Department of Acupuncture & Moxibustion, Dongguk University Bundang Oriental Hospital, Seongnam, Republic of Korea; 6Department of Acupuncture & Moxibustion Medicine, College of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Yong-Hyeon Baek, Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea, Tel +82 2 440 6099, Fax +82 2 440 7143, Email byhacu@khu.ac.krBackground: The aim of the present study is to confirm the efficacy, safety, and cost-effectiveness of thread-embedding acupuncture (TEA) in the treatment of adhesive capsulitis (AC).Methods: This is a randomized, sham-controlled, patient-assessor blinded trial with two parallel arms in a 1:1 ratio. A total of 160 participants with AC, also known as frozen shoulder, will be recruited and screened according to the eligibility criteria. Those who meet the eligibility criteria will be randomly allocated to a TEA group or a sham TEA (STEA) group. Both groups will receive either real TEA or thread-removed STEA treatment on nine acupoints once a week for 8 weeks while being blinded to the intervention. The shoulder pain and disability index will be evaluated as a primary outcome measure. In addition, a 100-mm pain visual analogue scale, rotator cuff quality of life scale, European Quality of Life 5-dimension 5-level scale, treatment satisfaction, safety assessment, and economic evaluation will be assessed as secondary outcome measures. Outcome assessments will be conducted for a total of 24 weeks, including a treatment period of 8 weeks and follow-up of 16 weeks, according to the schedule.Discussion: The results of this trial will provide a clinical basis for the efficacy, safety and cost-effectiveness of TEA in the treatment of patients with AC.Trial Registration Number: KCT0005920 (Clinical Research Information Service of the Republic of Korea). Registered on 22 February 2021.Keywords: thread-embedding acupuncture, adhesive capsulitis, frozen shoulder, randomized controlled trial, protocol

Leadership development experiences have long been touted as necessary and positive for promoting the practice of effective leadership. Yet, little has been presented about the effectiveness of leadership development programs sponsored, designed, and implemented by membership-based organizations, like fraternities and sororities. This study examines the efficacy of a national fraternity sponsored leadership development program for chapter presidents in facilitating a meaningful developmental experience and encouraging long-term learning gains. Data collected at three intervals throughout the year in which program attendees were in office were analyzed using ANOVA and t-tests to identify the specific areas in which students reported learning gains and then measured examining the extent to which learning was retained.

Greg D Fliney,1,* Eliott Kim,2,* Miriam Sarwana,3 Sze Wong,2 Tak Yee Tania Tai,2 Ji Liu,1 Soshian Sarrafpour,1 Nisha Chadha,2 Christopher C Teng1 1Yale University School of Medicine, Department of Ophthalmology and Visual Science, New Haven, CT, USA; 2Icahn School of Medicine at Mount Sinai/New York Eye and Ear, Eye and Vision Research Institute, New York, NY, USA; 3BCT Partners, Newark, NJ, USA*These authors contributed equally to this workCorrespondence: Christopher C Teng, Yale University School of Medicine, Department of Ophthalmology and Visual Science, 40 Temple Street Suite 3D, New Haven, CT, 06510, USA, Tel +1 203-785-2020, Fax +1 203-7856220, Email christopher.teng@yale.eduPurpose: To compare the safety and efficacy of Kahook Dual Blade (KDB) versus Trabectome with cataract surgery in reducing intraocular pressure (IOP) and medications used by patients with glaucoma.Methods: Retrospective chart review comparing eyes after KDB or Trabectome with cataract surgery at 2 academic centers. Surgical success was defined as IOP < 21 mmHg with ≥ 20% IOP reduction at post-operative month 12 (POM12). Changes in IOP, number of glaucoma medications, and adverse events were assessed.Results: Ninety eyes in the KDB group and 125 eyes in the Trabectome group were included. Mean changes in IOP at POM12 were − 1.9 ± 4.9 mmHg (11.2%, P = 0.002) in the KDB group and − 3.5 ± 5.5 mmHg (19.1%, P < 0.001) in the Trabectome group, without a significant difference between the groups (P = 0.20). Mean change in glaucoma medications at POM12 was − 0.8 ± 1.5 in the KDB group (58%, P < 0.001) and − 0.3 ± 1.3 (38%, P = 0.003) in the Trabectome group, with KDB having a greater decrease in medications (P = 0.02). The percentage of eyes achieving success was 30% for the KDB group and 54% for the Trabectome group (P = 0.01). Hyphema was the most common complication, with an incidence of 3% for the KDB group and 14% for the Trabectome group (P = 0.01).Conclusion: KDB or Trabectome with cataract surgery is safe and effective at lowering IOP and medication burden, with KDB resulting in a greater reduction in medications and Trabectome more frequently achieving success with an increased incidence of hyphema. Considering the study’s limitations, the outcomes were similar.Keywords: Kahook Dual Blade, Trabectome, goniotomy, minimally invasive glaucoma surgery

Abstract The first synthesis of organic Tri 6 Di 9 cages is presented. Two structurally distinct Tri 6 Di 9 cages were synthesised by combining a highly fluorinated aldehyde with two ditopic amines. Although the pure compounds could not be isolated despite many attempts, the information obtained is critical for the future design of large supramolecular structures. Computational and experimental methods indicate that the addition of perfluorinated aromatic linkers in the assembly of porous organic cages opens up new possibilities for influencing the reaction pathway towards rare and unknown structures.

The quantity and complexity of data being generated and published in biology has increased substantially, but few methods exist for capturing knowledge about phenotypes derived from molecular interactions between diverse groups of species, in such a way that is amenable to data-driven biology and research. To improve access to this knowledge, we have constructed a framework for the curation of the scientific literature studying interspecies interactions, using data curated for the Pathogen–Host Interactions database (PHI-base) as a case study. The framework provides a curation tool, phenotype ontology, and controlled vocabularies to curate pathogen–host interaction data, at the level of the host, pathogen, strain, gene, and genotype. The concept of a multispecies genotype, the ‘metagenotype,’ is introduced to facilitate capturing changes in the disease-causing abilities of pathogens, and host resistance or susceptibility, observed by gene alterations. We report on this framework and describe PHI-Canto, a community curation tool for use by publication authors.

Targeted radionuclide therapy (TRT) is an emerging field and has the potential to become a major pillar in effective cancer treatment. Several pharmaceuticals are already in routine use for treating cancer, and there is still a high potential for new compounds for this application. But, a major issue for many radiolabeled low-to-moderate-molecular-weight molecules is their clearance via the kidneys and their subsequent reuptake. High renal accumulation of radioactive compounds may lead to nephrotoxicity, and therefore, the kidneys are often the dose-limiting organs in TRT with these radioligands. Over the years, different strategies have been developed aiming for reduced kidney retention and enhanced therapeutic efficacy of radioligands. In this review, we will give an overview of the efforts and achievements of the used strategies, with focus on the therapeutic potential of low-to-moderate-molecular-weight molecules. Among the strategies discussed here is coadministration of compounds that compete for binding to the endocytic receptors in the proximal tubuli. In addition, the influence of altering the molecular design of radiolabeled ligands on pharmacokinetics is discussed, which includes changes in their physicochemical properties and implementation of cleavable linkers or albumin-binding moieties. Furthermore, we discuss the influence of chelator and radionuclide choice on reabsorption of radioligands by the kidneys.

Implementing smart microgrids for Non-Interconnected Zones (NIZs) has become an alternative solution to provide electrical energy by taking advantage of the resources available through the generation of renewable energy within these isolated areas. Within this context, in this study, the challenges related to microgrids and data analysis are presented, and different relevant data architectures described in the literature are compared. This paper focuses on the design of a data architecture for a smart microgrid for NIZs whose microgrid contains two 260 W solar panels, a 480 W inverter, and two 260 Ah batteries. Regarding the Colombian context, this paper describes the limitations (connectivity, isolation, appropriation of technologies) and opportunities (low demand, access to natural resources, state interest) from which the functional and non-functional requirements for the architecture are established. Finally, a data architecture is proposed and implemented in a NIZ in Colombia, and this paper also includes a description of the architecture, its characteristics, its associated opportunities and challenges, and discussions regarding its implementation.

The heterogeneity underlying cancer organoid phenotypes is not yet well understood. Here, the authors develop an imaging analysis assay for high throughput phenotypic screening of colorectal organoids that allows to define specific morphological changes that occur following different drug treatments.

Aqueous organic redox flow batteries are promising for grid-scale energy storage, although their practical application is still limited. Here, the authors report highly ion-conductive and selective polymer membranes, which boost the battery’s efficiency and stability, offering cost-effective electricity storage.

BackgroundPrimary hemophagocytic lymphohistiocytosis (pHLH) is an inherited inflammatory syndrome driven by the exuberant activation of interferon-gamma (IFNg)-producing CD8 T cells. Towards this end, ruxolitinib treatment or IFNg neutralization (aIFNg) lessens immunopathology in a model of pHLH in which perforin-deficient mice (Prf1–/–) are infected with Lymphocytic Choriomeningitis virus (LCMV). However, neither agent completely eradicates inflammation. Two studies combining ruxolitinib with aIFNg report conflicting results with one demonstrating improvement and the other worsening of disease manifestations. As these studies used differing doses of drugs and varying LCMV strains, it remained unclear whether combination therapy is safe and effective.MethodsWe previously showed that a ruxolitinib dose of 90 mg/kg lessens inflammation in Prf1–/– mice infected with LCMV-Armstrong. To determine whether this dose controls inflammation induced by a different LCMV strain, we administered ruxolitinib at 90mg/kg to Prf1–/– mice infected with LCMV-WE. To elucidate the impacts of single agent versus combination therapy, Prf1–/– animals were infected with LCMV, treated or not with ruxolitinib, aIFNg or both agents, and analyzed for disease features and the transcriptional impacts of therapy within purified CD8 T cells.ResultsRuxolitinib is well-tolerated and controls disease regardless of the viral strain used. aIFNg, administered alone or with ruxolitinib, is most effective at reversing anemia and reducing serum IFNg levels. In contrast, ruxolitinib appears better than aIFNg, and equally or more effective than combination therapy, at lessening immune cell expansion and cytokine production. Each treatment targets distinct gene expression pathways with aIFNg downregulating IFNg, IFNa, and IL-6-STAT3 pathways, and ruxolitinib downregulating IL-6-STAT3, glycolysis, and reactive oxygen species pathways. Unexpectedly, combination therapy is associated with upregulation of genes driving cell survival and proliferation.ConclusionsRuxolitinib is tolerated and curtails inflammation regardless of the inciting viral strain and whether it is given alone or in combination with aIFNg. When administered at the doses used in this study, the combination of ruxolitinb and aIFNg appears no better than treatment with either drug alone in lessening inflammation. Further studies are warranted to elucidate the optimal doses, schedules, and combinations of these agents for the treatment of patients with pHLH.

Familial hemophagocytic lymphohistiocytosis (fHLH) encompasses a group of rare inherited immune dysregulation disorders characterized by loss-of-function mutations in one of several genes involved in the assembly, exocytosis, and function of cytotoxic granules within CD8+ T cells and natural killer (NK) cells. The resulting defect in cytotoxicity allows these cells to be appropriately stimulated in response to an antigenic trigger, and also impairs their ability to effectively mediate and terminate the immune response. Consequently, there is sustained lymphocyte activation, resulting in the secretion of excessive amounts of pro-inflammatory cytokines that further activate other cells of the innate and adaptive immune systems. Together, these activated cells and pro-inflammatory cytokines mediate tissue damage that leads to multi-organ failure in the absence of treatment aimed at controlling hyperinflammation. In this article, we review these mechanisms of hyperinflammation in fHLH at the cellular level, focusing primarily on studies performed in murine models of fHLH that have provided insight into how defects in the lymphocyte cytotoxicity pathway mediate rampant and sustained immune dysregulation.

Structural disorder in materials is challenging to characterise. Here, the authors use multivariate analysis of atomic pair distribution functions to study structural collapse and melting of metal–organic frameworks, revealing powerful mechanistic and kinetic insight.

Eunseop Kim,1 Hye Won Lee,2 Namhyoung Kim,1 Young Hee Park,3 Tae-Young Choi,4 Myeong Soo Lee4 1You and Green Korean Medicine Clinic, Daejeon, South Korea; 2KM Convergence Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South Korea; 3You and Green Korean Medicine Clinic, Busan, South Korea; 4KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, South KoreaCorrespondence: Myeong Soo Lee, KM Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, South Korea, Tel +82-42-868-9266, Fax +82-42-868-9299, Email drmslee@gmail.com; mslee@kiom.re.kr Hye Won Lee, KM Convergence Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, South Korea, Tel +82-42-868-9506, Fax +82-42-868-9299, Email hwlee@kiom.re.krPurpose: Few studies have assessed outcomes associated with the use of traditional medicine therapies to manage infertility in clinical practice. The aim of this study was to investigate the clinical characteristics of and infertility treatment effects among patients who visited a Korean medicine (KM) clinic to aid in achieving pregnancy. This study consisted of a 10-year analysis of patient records from a KM clinic.Methods: A retrospective 10-year (2010– 2020) chart analysis was performed using the medical records of infertile patients who visited a KM clinic in South Korea for fertility treatment (ICD-10, infertility symptoms: 59 codes).Results: Of the 6194 patients who visited the clinic during the selected time frame, 1786 were female patients seeking fertility treatment to achieve pregnancy. Among the 1786 infertile women, 586 women succeeded in becoming pregnant (32.8%). Among the 586 patients who became pregnant, 476 women had received KM, 92 had been treated using KM and in vitro fertilization (IVF), and 18 had received KM and undergone intrauterine insemination (IUI). The live birth rates achieved with these treatments were 66.0%, 68.8%, and 66.7%, respectively. The most frequently prescribed medicines were Gamiboher-tang (Jiaweiwuxu-tang), Gamiguibi-tang (Jiaweiguipi-tang), and Gamidanggui-san (Jiaweidanggui-san). Additionally, the most frequent adjunct therapies administered to these patients were acupuncture and moxibustion.Conclusion: Infertility therapies using KM may be a successful option to treat infertility when used alone or in addition to IVF and IUI. However, further pharmacological investigations and clinical trials are required to ensure the objectivity of the efficacy evaluation.Keywords: herbal medicine, infertility, pregnancy, pregnancy rate, fertilization in vitro, retrospective studies

The current mixed-method study investigates transformational leadership qualities through higher education doctoral programs in the Commonwealth of Virginia. This study relies on three data points: interviews with graduate program directors of higher education doctoral programs (whether PhD or EdD), a program evaluation of programs, and Multifactor Leadership Questionnaire (MLQ-5x™) survey results from students within said programs. Data were collected from the five public universities that offer higher education doctoral programs within the Commonwealth of Virginia. Students completed a self-rating using the Multifactor Leadership Questionnaire (MLQ-5x™) and then were peer-rated by colleagues to strengthen the validity of the study. Additionally, themes surrounding the structures of these doctoral programs were collected. As researchers of higher education and leadership studies cite transformational leadership as a high competency for college and university presidents, coupled with a looming shortage of college and university presidents on the horizon, measuring the programs that train these potential future leaders is warranted.

We examined the impact of artisan cooperatives on East African women related to changes in consumer perception and food choice. We sought to understand how artisan cooperatives were impacting women’s food security, diet, and nutrition. To comprehend the lived experiences of women, a qualitative, phenomenological study was conducted within three purposively selected cooperatives in Rwanda and Kenya. Data was collected using Rapid Rural Appraisal (RRA) methodologies with three activities. When given a choice, women did not always eat healthier despite having more money and information about healthy diets. Diets shifted to include more sugar and fruit but less vegetables. Culture and location impacted how they cooked, what food was available to them, and what foods they chose to consume. Women explained how a higher income provided greater agency when buying food. It is crucial to comprehend how culture affects a person’s diet before implementation of nutrition programs. Further research is needed to determine if cooperatives geared toward women’s empowerment and economic sustainability can enhance the nutritional benefits of increased income in culturally relevant ways. This study has implications regarding sustainable development goals with international development programs that utilize locally sourced foods and are culturally viable.

Hoon Choi,1 Chul Soo Park,1 Jaewon Huh,1 Jungmin Koo,1 Joonpyo Jeon,2 Eunsung Kim,1 Sangmin Jung,1 Hwan Wook Kim,3 Ju Yong Lim,3 Wonjung Hwang1 1Department of Anesthesia and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Department of Anesthesia and Pain Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Department of Thoracic and Cardiovascular Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Wonjung HwangDepartment of Anesthesia and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea, Tel +82-2-22586162, Fax +82-2-5371951, Email amoeba79@catholic.ac.krPurpose: Postoperative delirium (POD) is a common but serious complication after cardiac surgery and is associated with various short- and long-term outcomes. In this study, we investigated the effects of intraoperative glycemic variability (GV) and other glycemic variables on POD after cardiac surgery.Patients and Methods: A retrospective single-center cohort analysis was conducted using data from electronic medical record from 2018 to 2020. A total of 705 patients undergoing coronary artery bypass graft surgery and/or valve surgery, and/or aortic replacement surgery were included in the analysis. Intraoperative GV was assessed with a coefficient of variation (CV), which was defined as the standard deviation of five intraoperative blood glucose measurements divided by the mean. POD assessment was performed three times a day in the ICU and twice a day in the ward until discharge by trained medical staff. POD was diagnosed if any of the Confusion Assessment Method for the Intensive Care Unit was positive in the ICU, and the Confusion Assessment Method was positive in the ward. Multivariable logistic regression was used to identify associations between intraoperative GV and POD.Results: POD occurred in 306 (43.4%) patients. When intraoperative glycemic CV was compared as a continuous variable, the delirium group had higher intraoperative glycemic CV than the non-delirium group (22.59 [17.09, 29.68] vs 18.19 [13.00, 23.35], p < 0.001), and when intraoperative glycemic CV was classified as quartiles, the incidence of POD increased as intraoperative glycemic CV quartiles increased (first quartile 29.89%; second quartile 36.67%; third quartile 44.63%; and fourth quartile 62.64%, p < 0.001). In the multivariable logistic regression model, patients in the third quartile of intraoperative glycemic CV were 1.833 times (OR 1.833, 95% CI: 1.132– 2.967, p = 0.014), and patients in the fourth quartile of intraoperative glycemic CV were 3.645 times (OR 3.645, 95% CI: 2.235– 5.944, p < 0.001) more likely to develop POD than those in the first quartile of intraoperative glycemic CV.Conclusion: Intraoperative blood glucose fluctuation, manifested by intraoperative GV, is associated with POD after cardiac surgery. Patients with a higher intraoperative GV have an increased risk of POD.Keywords: postoperative delirium, cardiac surgery, glycemic variability, coefficient of variation

Porous molecular materials are constructed from molecules that assemble in the solid-state such that there are cavities or an interconnected pore network. It is challenging to control the assembly of these systems, as the interactions between the molecules are generally weak, and subtle changes in the molecular structure can lead to vastly different intermolecular interactions and subsequently different crystal packing arrangements. Similarly, the use of different solvents for crystallization, or the introduction of solvent vapour, can result in different polymorphs and pore networks being formed. It is difficult to uniquely describe the pore networks formed, and thus we analyse 1033 crystal structures of porous molecular systems to determine the underlying topology of their void spaces and potential guest diffusion networks. Material-agnostic topology definitions are applied. We use the underlying topological nets to examine whether it is possible to apply isoreticular design principles to porous molecular materials. Overall, our automatic analysis of a large dataset gives a general insight into the relationships between molecular topologies and the topological nets of their pore network. We show that while porous molecular systems tend to pack similarly to non-porous molecules, the topologies of their pore distributions resemble those of more prominent porous materials, such as metal–organic frameworks and covalent organic frameworks.

Diarrhea is an important cause of hospitalizations in Mozambique. However, little attention has been paid to the impact HIV infection on the prevalence or clinical manifestations of enteric bacterial infections. This study aimed to determine the prevalence of Salmonella spp., Shigella spp. and Campylobacter spp. in HIV-infected and HIV-uninfected patients with diarrhea, identify risk factors for infection, and explore the association between HIV status, viral load, and bacterial prevalence. We conducted a case-control study at the Centro de Saúde de Mavalane and Centro de Saúde 1° de Maio in Maputo, Mozambique, from November 2021 to May 2022. We recruited 300 patients, including 150 HIV-infected (cases) and 150 HIV-uninfected patients (controls), aged between 0-88 years, presenting with diarrhea. Stool samples were collected for bacterial isolation through culture, and for each HIV-infected patient, 4 ml of venous blood were obtained for viral load detection through PCR. A total of 129 patients (43.0%) had at least one bacterial infection. The prevalence of Salmonella spp., Shigella spp. and Campylobacter spp. was 33.0% (n = 99), 15.0% (n = 45) and 4.3% (n = 13), respectively. The prevalence of any bacterial infection did not differ significantly between HIV-infected (45.3%, n = 68) and HIV-uninfected patients (40.7%, = 61) (p = 0.414). Overall, having 2-3 symptoms of enteric disease (p = 0.008) and a basic education (p = 0.030) were factors associated with bacterial infection. Of the 148 patients for whom HIV-1 RNA levels were available, 115 had copy numbers ≤ 75. Another 13 had levels between 76 and 1,000 and the remaining 20 had an average of 327,218.45 copies/ml. Bivariate logistic regression found that Shigella spp. were associated with HIV (p = 0.038), although no association was found in the multivariate analysis. Enteric infections are common in both HIV-infected and -uninfected patients. Low schooling influences the occurrence of enteric infections, which highlights the need to raise awareness about their prevention.

Royal jelly and honey are two substances produced successively by the worker bee caste. Modern proteomics approaches have been used to explore the protein component of each substance independently, but to date none have quantitatively compared the protein profile of honey and royal jelly directly. Sequential window acquisition of all theoretical fragment-ion spectra mass spectrometry (SWATH-MS) was used to compare protein quantities of bee origin in mānuka and clover honey to royal jelly. Two analysis techniques identified 76 proteins in total. Peptide intensity was directly compared for a subset of 31 proteins that were identified with high confidence, and the relative changes in protein abundance were compared between each honey type and royal jelly. Major Royal Jelly Proteins (MRJPs) had similar profiles in both honeys, except MRJP6, which was significantly more abundant in clover honey. Proteins involved in nectar metabolism were more abundant in honey than in royal jelly as expected. However, the trend revealed a potential catalytic role for MRJP6 in clover honey and a nectar- or honey-specific role for uncharacterised protein LOC408608. The abundance of MRJP6 in mānuka honey was equivalent to royal jelly suggesting a potential effect of nectar type on expression of this protein. Data are available via ProteomeXchange with identifier PXD038889.

Abstract Background Knowledge of the clinical and magnetic resonance imaging (MRI) features of intracranial Coccidioides infection in dogs is essential for prompt diagnosis to limit disease‐associated morbidity and death. Objectives To describe the MRI appearance of intracranial coccidioidomycosis in dogs, identify associated clinical and clinicopathologic findings, and report outcomes of medical treatment. Animals Forty‐five client‐owned dogs with presumed intracranial Coccidioides infection. Methods Retrospective case series. Medical records and images were reviewed. Clinical history, examination findings, serology, imaging characteristics, treatment, and outcome were recorded. Included cases had an abnormal brain MRI and positive Coccidioides serology by agar‐gel‐immunodiffusion (AGID). Results Median age was 7‐years. Generalized tonic‐clonic seizures were the most common presenting sign (25/45). Two lesion categories were identified: a granulomatous form with 1 or more distinct, intra‐axial, contrast‐enhancing foci (37/45), and a second variation with diffuse, bilateral, symmetrical lesions of the caudate nuclei and frontal lobes (8/45). Serum IgG titers ranged from 1 : 1 to ≥ 1 : 256; 2 dogs had positive IgM titers at 1 : 2. All dogs with follow‐up serology (34/45) had a reduction in titer. Mean duration of follow‐up was 22.4 ± 20.5 months (median 16 months). Six dogs were lost to follow‐up 1‐year. Of the remaining 34 dogs, 28 (82%) were alive ≥ 1‐year after diagnosis. Thirteen of these dogs had follow‐up times ≥ 2‐years. Conclusions and Clinical Importance The prognosis for intracranial Coccidioides infection is generally more favorable with medical treatment than in earlier reports.