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ABSTRACTHerpes zoster (HZ) is a prevalent disease characterized by a painful rash. A multi‑country study was conducted to elicit public and physician knowledge, attitude, and practice (KAP) toward HZ disease and vaccination for the assessment of local factors influencing HZ vaccine perceptions in four Asian-Pacific countries/territories One-to-one qualitative interviews were conducted in 2022, among the public (people aged ≥ 50 years, adults with parents aged ≥ 50 years, zoster vaccine live-vaccinated individuals aged ≥ 50 years in Republic of Korea, and HZ patients; n = 78) and physicians (general practitioners and specialists; n = 24). Themes surrounding KAP toward HZ and HZ vaccination were summarized using a thematic analysis. A substantial knowledge gap related to HZ was observed among the public, including its causes, long-term impacts, and the at-risk population. There was a low perceived risk of HZ and low general awareness of HZ vaccine availability, although country/territory-specific differences existed. Fear of HZ-associated pain contributed toward vaccination intent among HZ patients and adults with parents aged ≥ 50 years. HZ-naïve adults who were encouraged to receive the vaccine by others were not motivated to do so due to optimism bias. Physicians were perceived to be a reliable source of information. However, physicians did not always proactively discuss HZ vaccination due to time constraints and a perceived need to prioritize other vaccinations including influenza and pneumococcal vaccines. Initiatives are needed to improve public awareness of HZ and its complications, in terms of overall impact on individuals and society, and highlight the important role of physicians in recommending vaccination.

Abstract The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., −0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.

Nowadays there are multiple types of contraceptive methods, from reversible to permanent, for those choosing to delay pregnancy. Misconceptions about contraception and infertility are a key factor for discontinuation or the uptake of family planning methods. Regaining fertility (the ability to conceive) after contraceptive discontinuation is therefore pivotal. Technical studies to date have evaluated return to fertility by assessing pregnancy as an outcome, with variable results, or return to ovulation as a surrogate measure by assessing hormone levels (such as progesterone, LH, FSH) with or without transvaginal ultrasound. In general, relying on time to pregnancy as an indicator of return to fertility following contraceptive method discontinuation can be problematic due to variable factors independent of contraceptive effects on fertility, hormone clearance, and fertility recovery. Since the ability to conceive after contraceptive method discontinuation is a critical factor influencing product uptake, it is important to have robust biomarkers that easily and accurately predict the timing of fertility return following contraception and isolate that recovery from extrinsic and circumstantial factors. The main aim of this review is to summarize the current approaches, existing knowledge, and gaps in methods of evaluating return-to-fertility as well as to provide insights into the potential of new biomarkers to more accurately predict fertility restoration after contraceptive discontinuation. Biomarker candidates proposed in this document include those associated with folliculogenesis, cumulus cell expansion, follicular rupture and ovulation, and endometrial transport and receptivity which have been selected and scored on predefined criteria meant to evaluate their probable viability for advancement. The review also describes limitations, regulatory requirements, and a potential path to clinically testing these selected biomarkers. It is important to understand fertility restoration after contraceptive method discontinuation to provide users and health providers with accurate evidence-based information. Predictive biomarkers, if easy and low-cost, have the potential to enable robust evaluation of RTF, and provide potential users the information they desire when selecting a contraceptive method. This could lead to expanded uptake and continuation of modern contraception and inform the development of new contraceptive methods to widen user's family planning choices.

Cyclic AMP (cAMP) is a ubiquitous second messenger that transduces signals from cellular receptors to downstream effectors. Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, devotes a considerable amount of coding capacity to produce, sense, and degrade cAMP. Despite this fact, our understanding of how cAMP regulates Mtb physiology remains limited. Here, we took a genetic approach to investigate the function of the sole essential adenylate cyclase in Mtb H37Rv, Rv3645. We found that a lack of rv3645 resulted in increased sensitivity to numerous antibiotics by a mechanism independent of substantial increases in envelope permeability. We made the unexpected observation that rv3645 is conditionally essential for Mtb growth only in the presence of long-chain fatty acids, a host-relevant carbon source. A suppressor screen further identified mutations in the atypical cAMP phosphodiesterase rv1339 that suppress both fatty acid and drug sensitivity phenotypes in strains lacking rv3645. Using mass spectrometry, we found that Rv3645 is the dominant source of cAMP under standard laboratory growth conditions, that cAMP production is the essential function of Rv3645 in the presence of long-chain fatty acids, and that reduced cAMP levels result in increased long-chain fatty acid uptake and metabolism and increased antibiotic susceptibility. Our work defines rv3645 and cAMP as central mediators of intrinsic multidrug resistance and fatty acid metabolism in Mtb and highlights the potential utility of small molecule modulators of cAMP signaling.

Objectives: Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking. Methods: An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases. Results: 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively. Conclusion: The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Background: Operative treatment of displaced patella fracture dates back to Lister in 1877. Nowadays, steel wires remain the material of choice in tension band technique despite complications such as wire breakage, suboptimal placement, or skin impingement. We propose using a high-tensile strength braided tape-shaped polyblend suture (FiberTape®, Arthrex, Naples, Florida, USA) as an alternative that could minimize complications related to steel wires. Method: Between February 2014 and April 2018, 15 patients with displaced patella fractures (three distal pole, five transverse, and seven comminuted fractures) underwent our proposed method. Open fracture reduction was performed to optimize anatomy before figure-of-eight fixation with FiberTape®. An Ethibond-2 suture was also added as cerclage for stability. Postoperatively, an extension brace was given for wound resting, before progressing to mobilization exercises with a hinge-knee brace. At follow-ups, the knee’s range-of-motion (ROM), along with bone healing status from radiographs, was assessed. Results: The mean operation time was 84.5 min, and all surgeries were performed or supervised by the same senior surgeon. Eight patients were discharged from follow-up (mean follow-up of 9.9 months) after achieving good ROM and fracture healing. One patient defaulted, and the remaining is still being followed-up. There was no wound complication or knot impingement in all cases. One patient required manipulation under anesthesia due to stiffness, and one experienced malunion due to poor compliance to rehabilitation protocol. Conclusion: Fixation using a high-tensile strength braided suture may be an equally effective method in the management of displaced patella fracture. However, larger sample size is useful to provide a more definitive conclusion.

Summary: The Chinese ginseng Panax notoginseng is a domesticated herb with significant medicinal and economic value. Here we report a chromosome-level P. notoginseng genome assembly with a high (∼79%) repetitive sequence content. The juxtaposition with the widely distributed, closely related Korean ginseng (Panax ginseng) genome revealed contraction of plant defense genes (in particular R-genes) in the P. notoginseng genome. We also investigated the reasons for the larger genome size of Panax species, revealing contributions from two Panax-specific whole-genome duplication events and transposable element expansion. Transcriptome data and comparative genome analysis revealed the candidate genes involved in the ginsenoside synthesis pathway. We also performed a genome-wide association study on 240 cultivated P. notoginseng individuals and identified the associated genes with dry root weight (63 genes) and stem thickness (168 genes). The P. notoginseng genome represents a critical step toward harnessing the full potential of an economically important and enigmatic plant.

Abstract The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. To investigate their properties, we isolated glia and neurons from Cln3-deficient mice and studied their basic biology in culture. Upon stimulation, both Cln3-deficient astrocytes and microglia also showed an attenuated ability to transform morphologically, and an altered protein secretion profile. These defects were more pronounced in astrocytes, including the reduced secretion of a range of neuroprotective factors, mitogens, chemokines and cytokines, in addition to impaired calcium signalling and glutamate clearance. Cln3-deficient neurons also displayed an abnormal organization of their neurites. Most importantly, using a co-culture system, Cln3-deficient astrocytes and microglia had a negative impact on the survival and morphology of both Cln3-deficient and wildtype neurons, but these effects were largely reversed by growing mutant neurons with healthy glia. These data provide evidence that CLN3 disease astrocytes are functionally compromised. Together with microglia, they may play an active role in neuron loss in this disorder and can be considered as potential targets for therapeutic interventions.

Abstract Background We sought to identify spatial/dosimetric patterns of failure for oral cavity cancer patients receiving post-operative IMRT (PO-IMRT). Methods Two hundred eighty-nine OCC patients receiving PO-IMRT were retrospectively reviewed from 2000 to 2012. Diagnostic CT documenting recurrence (rCT) was co-registered with planning CT (pCT) using a validated deformable image registration software. Manually segmented recurrent gross disease (rGTV) was deformed to co-registered pCTs. Mapped rGTVs were compared dosimetrically to planned dose and spatially to planning target volumes using centroid-based approaches. Failures types were classified using combined spatial/dosimetric criteria: A (central high-dose), B (peripheral high-dose), C (central intermediate/low-dose), D (peripheral intermediate/low-dose), and E (extraneous-dose). Results Fifty-four patients with recurrence were analyzed; 26 local recurrence, 19 regional recurrence, and 9 both local and regional recurrence. Median time to recurrence was 4 months (range 0–71). Median rGTVs volume was 3.7 cm3 (IQR 1.4–10.6). For spatial and dosimetric analysis of the patterns of failure, 30 patients (55.5%) were classified as type A (central high-dose). Non-central high dose failures were distributed as follows: 2 (3.7%) type B, 10 (18.5%) type C, 1 (1.8%) type D, and 9 (16.7%) type E. Non-IMRT failure in the matching low-neck field was seen in two patients. No failures were noted at the IMRT-supraclavicular field match-line. Conclusions Approximately half of patients with local/regional failure had non-central high dose recurrence. Peripheral high dose misses were uncommon reflecting adequate delineation and dose delivery. Future strategies are needed to reduce types C and E failures.

The integration of biomaterials and understanding of vascular biology has led to the development of perfusable endothelialized flow models, which have been used as valuable tools to study the platelet–endothelium interface under shear. In these models, the parameters of geometry, compliance, biorheology, and cellular complexity are varied to recapitulate the physical biology of platelet recruitment and activation under physiologically relevant conditions of blood flow. In this review, we summarize the mechanistic insights learned from perfusable microvessel models and discuss the potential utility as well as challenges of endothelialized microfluidic devices to study platelet function in the bloodstream in vitro.

Introduction: As providers transition from “fee-for-service” to “pay-for-performance” models, focus has shifted to improving performance. This trend extends to the emergency department (ED) where visits continue to increase across the United States. Our objective was to determine whether displaying public performance metrics of physician triage data could drive intangible motivators and improve triage performance in the ED. Methods: This is a single institution, time-series performance study on a physician-in-triage system. Individual physician baseline metrics—number of patients triaged and dispositioned per shift—were obtained and prominently displayed with identifiable labels during each quarterly physician group meeting. Physicians were informed that metrics would be collected and displayed quarterly and that there would be no bonuses, punishments, or required training; physicians were essentially free to do as they wished. It was made explicit that the goal was to increase the number triaged, and while the number dispositioned would also be displayed, it would not be a focus, thereby acting as this study’s control. At the end of one year, we analyzed metrics. Results: The group’s average number of patients triaged per shift were as follows: Q1–29.2; Q2–31.9; Q3–34.4; Q4–36.5 (Q1 vs Q4, p < 0.00001). The average numbers of patients dispositioned per shift were Q1–16.4; Q2–17.8; Q3–16.9; Q4–15.3 (Q1 vs Q4, p = 0.14). The top 25% of Q1 performers increased their average numbers triaged from Q1–36.5 to Q4–40.3 (ie, a statistically insignificant increase of 3.8 patients per shift [p = 0.07]). The bottom 25% of Q1 performers, on the other hand, increased their averages from Q1–22.4 to Q4–34.5 (ie, a statistically significant increase of 12.2 patients per shift [p = 0.0013]). Conclusion: Public performance metrics can drive intangible motivators (eg, purpose, mastery, and peer pressure), which can be an effective, low-cost strategy to improve individual performance, achieve institutional goals, and thrive in the pay-for-performance era.

Statin-associated necrotizing autoimmune myositis (NAM) is an autoimmune condition characterized by severe acute-onset proximal muscle weakness, a very high creatinine kinase (CK) level, and prominent myofiber necrosis and minimal lymphocytic infiltration on muscle biopsy. Unlike self-limited statin myopathy, this condition usually requires aggressive immunomodulation therapy to assist recovery and prevent future disability. In this case report, we present a patient who developed progressive muscle weakness after taking atorvastatin for one year. At initial presentation, her CK level was 28,000 U/L. She was diagnosed with statin-associated NAM and started on high-dose intravenous solumedrol, mycophenolate, and intravenous immunoglobulin (IVIG) therapy. However, she subsequently developed acute bilateral vision loss and right side hemineglect; she was diagnosed with posterior reversible encephalopathy syndrome (PRES), thought to be a possible delayed adverse reaction to IVIG. IVIG was discontinued, and the patient was treated with supportive therapy. At six-month follow-up, she had significant improvement in muscle strength and vision.

Radiomics leverages existing image datasets to provide non-visible data extraction via image post-processing, with the aim of identifying prognostic, and predictive imaging features at a sub-region of interest level. However, the application of radiomics is hampered by several challenges such as lack of image acquisition/analysis method standardization, impeding generalizability. As of yet, radiomics remains intriguing, but not clinically validated. We aimed to test the feasibility of a non-custom-constructed platform for disseminating existing large, standardized databases across institutions for promoting radiomics studies. Hence, University of Texas MD Anderson Cancer Center organized two public radiomics challenges in head and neck radiation oncology domain. This was done in conjunction with MICCAI 2016 satellite symposium using Kaggle-in-Class, a machine-learning and predictive analytics platform. We drew on clinical data matched to radiomics data derived from diagnostic contrast-enhanced computed tomography (CECT) images in a dataset of 315 patients with oropharyngeal cancer. Contestants were tasked to develop models for (i) classifying patients according to their human papillomavirus status, or (ii) predicting local tumor recurrence, following radiotherapy. Data were split into training, and test sets. Seventeen teams from various professional domains participated in one or both of the challenges. This review paper was based on the contestants' feedback; provided by 8 contestants only (47%). Six contestants (75%) incorporated extracted radiomics features into their predictive model building, either alone (n = 5; 62.5%), as was the case with the winner of the “HPV” challenge, or in conjunction with matched clinical attributes (n = 2; 25%). Only 23% of contestants, notably, including the winner of the “local recurrence” challenge, built their model relying solely on clinical data. In addition to the value of the integration of machine learning into clinical decision-making, our experience sheds light on challenges in sharing and directing existing datasets toward clinical applications of radiomics, including hyper-dimensionality of the clinical/imaging data attributes. Our experience may help guide researchers to create a framework for sharing and reuse of already published data that we believe will ultimately accelerate the pace of clinical applications of radiomics; both in challenge or clinical settings.

This case describes a patient presenting with acute onset papilledema, subacute strokes resulting in upper extremity weakness and numbness, arthritis, maculopapular rash, depressed C4 and CH50, and a high titer anti-double-stranded DNA antibody. The patient was given the diagnosis of probable systemic lupus erythematosus, which was supported by the Systemic Lupus International Collaborating Clinics (SLICC) criteria. He was aggressively treated for neuropsychiatric lupus (NPSLE) with pulse dose steroids and a dose of intravenous cyclophosphamide. Blood cultures drawn on admission later grew out 2/4 bottles of Gram-variable bacteria, speciated as Brucella melitensis by PCR. Serum Brucella serologies were also positive. On further evaluation, the patient noted a history of eating unpasteurized cheese in Mexico. Given these additional findings, the patient’s presentation was most consistent with a diagnosis of neurobrucellosis. Steroids were tapered off, no further doses of cyclophosphamide were given, and a prolonged course of intravenous and oral antibiotic therapy was administered, resulting in complete resolution of the patient’s presenting symptoms.