A selective voting convex-hull ensemble procedure for personalized medicine.
Genes work in concert as a system as opposed to independent entities and mediate disease states. There has been considerable interest in understanding variations in molecular signatures between normal and disease states. However, a majority of techniques implicitly assume homogeneity between samples within a given group and use a fixed set of genes in discerning the groups. The proposed study overcomes these caveats by using a selective-voting convex-hull ensemble procedure that accommodates molecular heterogeneity within and between groups. The significance of the study is its potential to selectively retrieve sample-specific ensemble sets and investigate variations in the networks corresponding to the ensemble set across these samples. These characteristics fit well within the scope of personalized medicine and comparative effectiveness research that emphasize on patient-tailored interventions. While the results are demonstrated on colon cancer gene expression profiles the approach as such is generic and can be readily extended to other settings.


Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.
Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2) or the zinc-finger transcription factor lame duck (lmd) lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.


Submaximal inhibition of protein kinase C restores ADP-induced dense granule secretion in platelets in the presence of Ca2+.
Protein kinase C (PKC) is a family of serine/threonine kinases that play isoform-specific inhibitory and stimulatory roles in platelet activation. We show here that the pan-PKC inhibitor Ro31-8220 can be used to dissect these events following platelet activation by ADP. Submaximal concentrations of Ro31-8220 potentiated aggregation and dense granule secretion to ADP in plasma anticoagulated with citrate, in D-Phe-Pro-Arg-chloromethyl ketone-anticoagulated plasma, which has physiological levels of Ca(2+), and in washed platelets. Potentiation was retained on inhibition of cyclooxygenase and was associated with an increase in intracellular Ca(2+). Potentiation of aggregation and secretion was abolished by a maximally effective concentration of Ro31-8220, consistent with a critical role of PKC in secretion. ADP-induced secretion was potentiated in the presence of an inhibitor of PKCβ but not in the presence of available inhibitors of other PKC isoforms in human and mouse platelets. ADP-induced secretion was also potentiated in mouse platelets deficient in PKCε but not PKC. These results demonstrate that partial blockade of PKC potentiates aggregation and dense granule secretion by ADP in association with increased Ca(2+). This provides a molecular explanation for the inability of ADP to induce secretion in plasma in the presence of physiological Ca(2+) concentrations, and it reveals a novel role for PKC in inhibiting platelet activation by ADP in vivo. These results also demonstrate isoform-specific inhibitory effects of PKC in platelets.


Cloning and characterization of DNA sequences surrounding the human gamma-, delta-, and beta-globin genes.
The human gamma-, delta-, and beta-globin genes are located within a 30-kilobase (kb) region of DNA, of which only 20% represents the globin genes. We have attempted to define the nature of flanking and intergenic sequences by isolating recombinants containing the human epsilon, both gamma-, or the 3' end of the beta-globin gene from a bacteriophage library of cloned human DNA. Comparison of these recombinants and a recombinant containing the delta- and beta-globin genes (H beta G1) has provided the following results. The epsilon-globin gene is located 14 kb 5' to the G gamma gene. DNA sequence homology between the region containing the two G gamma genes and the delta nd beta gene region is limited to only a few hundred nucleotides which include the globin coding sequences. Repetitive DNA sequences have been found in the region 3' to the beta-globin gene. Sequences located adjacent to the beta-globin gene are repeated in the globin gene region. A repetitive DNA sequence more than 3.2 kb long is repeated frequently in the human genome but is not repeated in the globin gene region in the clones examined.


Improving survival in bacterial endocarditis.
Twenty six cases of bacterial endocarditis in infancy and childhood were treated with a mortality of less than 8%. Twenty two had recognised congenital heart disease and four had previously normal hearts. Thirteen out of the 24 cases with positive blood cultures had staphylococcal infection. Appropriate antibiotics were identified by measurement of the minimum bactericidal concentration as an indicator of antibiotic sensitivity. The bactericidal activity of the patient's serum during treatment was monitored by back titration against the causative organism to assess the optimal antibiotic combination and dosage. Treatment was continued for six weeks in most cases, comprising intravenous treatment for at least the first three weeks, but then being substituted with oral treatment in some. Twenty one cases were successfully treated medically. Five developed complications requiring surgery, two of whom died.


High-level expression of truncated surface antigen P50 of Babesia gibsoni in insect cells by baculovirus and evaluation of its immunogenicity and antigenicity.
Previously, we identified an immunodominant antigen, P50 of Babesia gibsoni. In the present study, the gene encoding the truncated P50 (rP50t) without a C-terminal hydrophobic region (29 amino acids [aa]) was expressed in insect cells by a recombinant baculovirus. The highly hydrophobic C-terminal 20-aa regions seems to be a transmembrane region, which was evidenced by the fact that rP50t was effectively secreted into the supernatant of insect cells infected with the recombinant baculovirus. N-terminal amino acid sequence analysis of rP50t indicated that N-terminal 19 aa function as a signal peptide. The expression level of rP50t reached up to 2 mg per 10(8) cells infected with the recombinant baculovirus. The immunogenic property of rP50t was evaluated by an immunization test in mice. Mice immunized with rP50t induced a high-level antibody titer against the B. gibsoni merozoite. Monoclonal antibodies (MAbs) to rP50t were produced in mice to determine the immunogenic regions of P50. The epitope(s) recognized by all five MAbs were located between aa 190 and 273, suggesting that the central part of P50 is a highly immunogenic region. The diagnostic potential of rP50t was evaluated using an enzyme-linked immunosorbent assay (ELISA). The ELISA was able to differentiate clearly (P < 0.0001) between B. gibsoni-infected dog serum and B. canis-infected dog serum or noninfected dog serum. Our results indicated that the rP50t may provide a useful potential immunogenic reagent for use in diagnosis and as a subunit vaccine to control B. gibsoni infection in dogs.


Malignant pleural mesothelioma: current and future perspectives.
Mesothelioma still remains an occupational related cancer with severe outcome. It is usually diagnosed at advanced stage since it does not demonstrate early symptoms. Several efforts have been made towards removing all materials inducing mesothelioma in the work setting and new work protection measures have been applied. Although we have new targeted treatments and radical surgery as arrows in the quiver, the type of mesothelioma and early diagnosis still remain the best treatment approach. Novel treatment modalities have been explored and several others are already on the way. In the current review we will present current data for mesothelioma and future perspectives.


High altitude pulmonary edema.
Altitude, speed and mode of ascent and, above all, individual susceptibility are the most important determinants for the occurrence of high-altitude pulmonary edema (HAPE). This illness usually occurs only 2-5 days after acute exposure to altitudes above 2,500-3,000 m. Chest radiographs and CT scans show a patchy predominantly peripheral distribution of edema. Wedge pressure is normal at rest, and there is an excessive rise in pulmonary artery pressure (Ppa) which precedes edema formation. Bronchoalveolar lavage in patients with advanced HAPE shows evidence of inflammatory response with increased capillary permeability. There are, however, no prospective data indicating whether the inflammatory response is a primary cause of HAPE or a consequence of edema formation. Excessive rise in Ppa appears to be a crucial pathophysiologic factor for HAPE. Recent observations of high Ppa in HAPE-susceptible subjects who did not develop pulmonary edema after rapid ascent to high altitude suggest either that Ppa does not necessarily reflect capillary pressure in these individuals or else that additional factors, such as an inflammatory response and/or a decreased fluid clearance from the lung, are necessary for the development of pulmonary edema. The treatment of choice is immediate descent. When this is impossible and supplemental oxygen is not available, treatment with nifedipine is recommended until descent is possible.


Surgical treatment of a giant left ventricular aneurysm- a case report.
An aneurysm of the left ventricle is a complication of acute myocardial infarction. We report a case of a giant aneurysm of the left ventricle after myocardial infarction in a 59 year-old male patient. The surgery to correct the aneurysm was performed with the use of cardiopulmonary bypass under normothermia. A bovine pericardial patch was used for the geometric reconstruction of the ventricular wall affected by the aneurysm. After the procedure, echocardiography and magnetic resonance imaging revealed improvement in left ventricular ejection fraction and volume reduction.


College students' perceptions of alcohol's role in disclosures of sexual assault and intimate partner violence.
Objective: Much is known about how alcohol increases the risk of sexual assault or intimate partner violence victimization during college. This research qualitatively explores perceptions about how alcohol influences disclosures about these events to informal supports. Participants: Participants included college students who received a disclosure wherein they or the survivor were drinking during the disclosure (n = 81). Methods: Responses were coded with regard to who was drinking and whether the effect of drinking during the disclosure was perceived as positive, negative, mixed, or neutral/none. Results: Participants perceived alcohol to have both positive (e.g., increasing the likelihood of discussing difficult topics) and negative (e.g., cognitive impairment increased negative emotions) effects on disclosures. Conclusion: Prevention and intervention efforts should identify targeted strategies (e.g., remembering one or two easy and helpful phrases; revisiting the topic again while sober) to help survivors and disclosure recipients have constructive conversations in the presence of alcohol.


Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS.
Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS-CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS-CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS-CoV-2 due to its similarities with SARS-CoV, and the disease as coronavirus disease-2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.


Biosynthesis of thiamin thiazole in eukaryotes: conversion of NAD to an advanced intermediate.
Thiazole synthase catalyzes the formation of the thiazole moiety of thiamin pyrophosphate. The enzyme from Saccharomyces cerevisiae (THI4) copurifies with a set of strongly bound adenylated metabolites. One of them has been characterized as the ADP adduct of 5-(2-hydroxyethyl)-4-methylthiazole-2-carboxylic acid. Attempts toward yielding active wild-type THI4 by releasing protein-bound metabolites have failed so far. Here, we describe the identification and characterization of two partially active mutants (C204A and H200N) of THI4. Both mutants catalyzed the release of the nicotinamide moiety from NAD to produce ADP-ribose, which was further converted to ADP-ribulose. In the presence of glycine, both the mutants catalyzed the formation of an advanced intermediate. The intermediate was trapped with ortho-phenylenediamine, yielding a stable quinoxaline derivative, which was characterized by NMR spectroscopy and ESI-MS. These observations confirm NAD as the substrate for THI4 and elucidate the early steps of this unique biosynthesis of the thiazole moiety of thiamin in eukaryotes.


Monoclonal gammopathy in a patient with chronic active hepatitis. A case report.
A case of chronic active hepatitis associated with monoclonal gammopathy (MG) is reported. In addition, the patient had Bence-Jones proteinuria, which is said to be an unusual finding in benign MG. Although a polyclonal increase in immunoglobulins is not uncommon in patients with liver disease, MG is relatively rare. No evidence of malignant disease was found in our patient, but it should be noted that numerous malignant disorders occur with increased frequency in patients with benign MG. A further reason for careful follow-up in these patients is that the paraproteinaemia itself may become malignant with time.


Global Challenges for Cancer Imaging.
Imaging plays many essential roles in nearly all aspects of high-quality cancer care. However, challenges to the delivery of optimal cancer imaging in both developing and advanced countries are manifold. Developing countries typically face dramatic shortages of both imaging equipment and general radiologists, and efforts to improve cancer imaging in these countries are often complicated by poor infrastructure, cultural barriers, and other obstacles. In advanced countries, on the other hand, although imaging equipment and general radiologists are typically accessible, the complexity of oncologic imaging and the need for subspecialists in the field are largely unrecognized; as a result, training opportunities are lacking, and there is a shortage of radiologists with the necessary subspecialty expertise to provide optimal cancer care and participate in advanced clinical research. This article is intended to raise awareness of these challenges and catalyze further efforts to address them. Some promising strategies and ongoing efforts are reviewed, and some specific actions are proposed.


Molecular recognition determinants for type IV secretion of diverse families of conjugative relaxases.
In preparation for transfer conjugative type IV secretion systems (T4SS) produce a nucleoprotein adduct containing a relaxase enzyme covalently linked to the 5' end of single-stranded plasmid DNA. The bound relaxase is expected to present features necessary for selective recognition by the type IV coupling protein (T4CP), which controls substrate entry to the envelope spanning secretion machinery. We prove that the IncF plasmid R1 relaxase TraI is translocated to the recipient cells. Using a Cre recombinase assay (CRAfT) we mapped two internally positioned translocation signals (TS) on F-like TraI proteins that independently mediate efficient recognition and secretion. Tertiary structure predictions for the TS matched best helicase RecD2 from Deinococcus radiodurans. The TS is widely conserved in MOB(F) and MOB(Q) families of relaxases. Structure/function relationships within the TS were identified by mutation. A key residue in specific recognition by T4CP TraD was revealed by a fidelity switch phenotype for an F to plasmid R1 exchange L626H mutation. Finally, we show that physical linkage of the relaxase catalytic domain to a TraI TS is necessary for efficient conjugative transfer.


An exploration of physiotherapists' experiences of robotic therapy in upper limb rehabilitation within a stroke rehabilitation centre.
Strokes are the world's leading cause of adult disability, with movement impairment being more common in the upper limb (UL). Robotic therapy (RT) is identified as an effective adjunct to promote movement but with limited effect on functional capabilities. There is currently limited research in user experience of RT, specifically that of physiotherapists. This study sought to explore physiotherapists' experience of using RT in rehabilitation of the UL, within a stroke rehabilitation centre in the north of England. Physiotherapists (n = 6) shared their experiences of working with the InMotion2 robot through semi-structured interviews. Thematic analysis was employed to interpret data, identify emergent themes and interdependent relationships between them. Five interdependent themes were identified focused around individualized care, influenced by evidence for practice, human relationships, skill mix, and resources and resource management. All physiotherapists valued the use of RT as an adjunct to conventional therapy, although barriers to successful implementation seemed to dominate the views of some. RT was perceived positively by physiotherapists, regarded as an adjunct to conventional therapy. A framework to summarize the relationships of participants' views and experiences is proposed in an attempt to understand the influences on the clinical use of RT. Implications for Rehabilitation Robotic therapy (RT) is valued as an adjunct to (conventional) person-centred rehabilitation. Resource management and skill mix are viewed as two key challenges to the successful implementation of RT. The production of evidence-based guidelines would be a useful development in the advancement.


Digital Support Systems to Improve Child Health and Development in Peru: Protocol for a Randomized Controlled Trial.
Children living in low and middle-income countries (LMICs) are at greater risk for experiencing adversities that can undermine their health and early development. Recently launched digital early childhood development (ECD) programs attempt to support families with young children in their home environments using digital technologies. However, relatively little is known regarding the effectiveness of these new technologies. The goal of this study is to rigorously assess the reach, effectiveness, and cost-effectiveness of a newly developed digital ECD platform called Afini. The Afini platform was designed to support parents of young children in low-resource settings to improve ECD and interact with caregivers through messenger services and a chatbot. This is a 3-arm cluster randomized controlled trial. In total, 2471 caregivers and their 3- to 9-month-old children were enrolled in the study across 164 study clusters in the San Marcos, Cajabamba, and Cajamarca provinces of Peru. Clusters of participants were randomly assigned to 1 of 3 groups: a control group (72 community clusters and 980 caregiver-child dyads), a home visit intervention group (20 community clusters and 316 caregiver-child dyads), and an Afini intervention group (72 community clusters and 1175 caregiver-child dyads). Families in the control group receive no focused ECD intervention. The home visit group is receiving biweekly home visits by a trained field staff following the national ECD program (Programa Nacional Cuna Más) curriculum and training guidelines. Caregivers in the Afini group are receiving ECD activities and advice through the digital platform. The primary study outcome is children's overall development at the age of 2.5 years, using the internationally validated long form of the Global Scales for Early Development. Secondary outcomes include caregiver engagement; caregiver mental health; screen time; as well as caregiver reports of children's motor, cognitive, language, and socioemotional development measured through locally piloted and validated tools. Enrollment started in September 2021 and ended in March 2023. Endline assessments will take place between August 2023 and September 2024. This study is, to our knowledge, the first to rigorously assess the effectiveness and cost-effectiveness of digital ECD technologies in LMICs. Given the large number of children in LMICs currently receiving only limited external support, the evaluated platform has the potential to improve the short- and long-term well-being of millions of children and their parents globally. ClinicalTrials.gov NCT05202106; https://clinicaltrials.gov/ct2/show/NCT05202106. DERR1-10.2196/50371.


Concurrent and predictive validity of the cognitive adaptive test/clinical linguistic and auditory milestone scale (CAT/CLAMS) and the Mental Developmental Index of the Bayley Scales of Infant Development.
The Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r = 0.393; p = 0.008) and 30 months (r = 0.742; p = 0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r = 0.181; p = 0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.


Autoionization of molecular hydrogen: where do the Fano lineshapes go?
Atomic autoionization following photoabsorption is a typical example of quantum interferences governed by electron-electron correlation. Coherence between direct photoionization and autoionization paths results in "Fano profiles", widely explored in atoms in the last 60 years. The advent of femto- and attosecond laser technology made time-resolved images of the delayed electron ejection in autoionization accessible, leading to the reemergence of such studies in atomic systems. The counterpart molecular phenomena show the richness, as well as the complexity, added by nuclear motion, which may proceed on similar time scales. However, Fano profiles are usually absent in measured molecular photoionization cross sections and an unequivocal parametrization of molecular autoionization signatures, similar to that introduced by Fano in atoms [U. Fano, Phys. Rev. 1961, 124, 1866] has not yet been achieved. In this work we introduce a simple semiclassical model that accounts for all the features observed in H2 photoionization and demonstrate that the interference structures observed in dissociative ionization spectra are almost exclusively due to the phase accumulated in the nuclear motion. Furthermore, we show that the temporal build-up of these structures in the energy-differential cross sections is also determined by nuclear motion. We validate our models by comparing with full-dimensional ab initio calculations solving the time-dependent Schrödinger equation.


Towards the Fundamental Quantum Limit of Linear Measurements of Classical Signals.
The quantum Cramér-Rao bound (QCRB) sets a fundamental limit for the measurement of classical signals with detectors operating in the quantum regime. Using linear-response theory and the Heisenberg uncertainty relation, we derive a general condition for achieving such a fundamental limit. When applied to classical displacement measurements with a test mass, this condition leads to an explicit connection between the QCRB and the standard quantum limit that arises from a tradeoff between the measurement imprecision and quantum backaction; the QCRB can be viewed as an outcome of a quantum nondemolition measurement with the backaction evaded. Additionally, we show that the test mass is more a resource for improving measurement sensitivity than a victim of the quantum backaction, which suggests a new approach to enhancing the sensitivity of a broad class of sensors. We illustrate these points with laser interferometric gravitational-wave detectors.


Third-line or fourth-line chemotherapy in non-small-cell lung cancer patients with relatively good performance status.
Our aim here was to explore treatment efficacy of pemetrexed and docetaxel in non-small-cell lung cancer patients who had failed previous chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor therapy. We retrospectively reviewed clinical data of our non-small-cell lung cancer patients who received third- or fourth-line chemotherapy with pemetrexed or docetaxel in our institution from January 2006 to December 2009. One hundred and twenty-three patients received treatment, including 85 patients with pemetrexed treatment and 38 patients with docetaxel treatment. There was no difference in tumor response rate and toxicity profiles when using pemetrexed as third- or fourth-line treatment, neither was there difference in docetaxel treatment of third- versus fourth-line treatment. There was also no difference between docetaxel and pemetrexed in response rate and control rate when they were used as fourth-line treatment. However, docetaxel used in fourth-line treatment had higher incidence of neutropenia and more frequent need of granulocyte colony-stimulating factor support compared with pemetrexed in fourth-line treatment. Median progression-free survivals (PFSs) were 2.6 months and 3.8 months when using pemetrexed as third- and fourth-line treatment, respectively (p = 0.417). Median PFSs were 3.8 months and 4.8 months when using docetaxel as third- and fourth-line treatment, respectively (p = 0.882). There was also no difference in PFS between pemetrexed and docetaxel, both in third- and fourth-line treatment. Median survivals were 13.4, 12.2, 13.2, and 13 months for pemetrexed in third-line, fourth-line, and docetaxel in third-line and fourth-line treatment, respectively. This retrospective study of pemetrexed and docetaxel showed relatively safe toxicity profile, reasonable response rate, and long survival when used as third- and fourth-line chemotherapy. Thus, it is reasonable to give good performance status patients third- and fourth-line chemotherapy. A phase III randomized trial is needed for better clarification of these issues.


Sex-related differences in the risk factors for in-hospital mortality and outcomes of ischemic stroke patients in rural areas of Taiwan.
Sex-related differences in the clinical presentation and outcomes of stroke patients are issues that have attracted increased interest from the scientific community. The present study aimed to investigate sex-related differences in the risk factors for in-hospital mortality and outcome in ischemic stroke patients. A total of 4278 acute ischemic stroke patients admitted to a stroke unit between January 1, 2007 and December 31, 2014 were included in the study. We considered demographic characteristics, clinical characteristics, co-morbidities, and complications, among others, as factors that may affect clinical presentation and in-hospital mortality. Good and poor outcomes were defined as modified Ranking Score (mRS)≦2 and mRS>2. Neurological deterioration (ND) was defined as an increase of National Institutes of Health Stroke Score (NIHSS) ≥ 4 points. Hemorrhagic transformation (HT) was defined as signs of hemorrhage in cranial CT or MRI scans. Transtentorial herniation was defined by brain edema, as seen in cranial CT or MRI scans, associated with the onset of acute unilateral or bilateral papillary dilation, loss of reactivity to light, and decline of ≥ 2 points in the Glasgow coma scale score. Of 4278 ischemic stroke patients (women 1757, 41.1%), 269 (6.3%) received thrombolytic therapy. The in hospital mortality rate was 3.35% (139/4278) [4.45% (80/1757) for women and 2.34% (59/2521) for men, p < 0.01]. At discharge, 41.2% (1761/4278) of the patients showed good outcomes [35.4% (622/1757) for women and 45.2% (1139/2521) for men]. Six months after stroke, 56.1% (1813/3231) showed good outcomes [47.4% (629/1328) for women and 62.2% (1184/1903) for men, p < 0.01]. Atrial fibrillation (AF), diabetes mellitus, stroke history, and old age were factors contributing to poor outcomes in men and women. Hypertension was associated with poor outcomes in women but not in men in comparison with patients without hypertension. Stroke severity and increased intracranial pressure were associated with increased in-hospital mortality in men and women. AF was associated with increased in-hospital mortality in women but not in men compared with patients without AF. The in-hospital mortality rate was not significantly different between women and men. Functional outcomes at discharge and six months after stroke were poorer in women than in men. Hypertension is an independent factor causing poorer outcomes in women than in men. AF is an independent factor affecting sex differences in hospital mortality in women.


Optical Flow Estimation Improves Automated Seizure Detection in Neonatal EEG.
Existing automated seizure detection algorithms report sensitivities between 43% and 77% and specificities between 56% and 90%. The algorithms suffer from false alarms when applied to neonatal EEG because of the high degree of nurse handling and rhythmic patting used to soothe neonates. Computer vision technology that quantifies movement in real time could distinguish artifactual motion and improve automated neonatal seizure detection algorithms. The authors used video EEG recordings from 43 neonates undergoing monitoring for seizures as part of the NEOLEV2 clinical trial. The Persyst neonatal automated seizure detection algorithm ran in real time during study EEG acquisitions. Computer vision algorithms were applied to extract detailed accounts of artifactual movement of the neonate or people near the neonate though dense optical flow estimation. Using the methods mentioned above, 197 periods of patting activity were identified and quantified, of which 45 generated false-positive automated seizure detection events. A binary patting detection algorithm was trained with a subset of 470 event videos. This supervised detection algorithm was applied to a testing subset of 187 event videos with 8 false-positive events, which resulted in a 24% reduction in false-positive automated seizure detections and a 50% reduction in false-positive events caused by neonatal care patting, while maintaining 11 of 12 true-positive seizure detection events. This work presents a novel approach to improving automated seizure detection algorithms used during neonatal video EEG monitoring. This artifact detection mechanism can improve the ability of a seizure detector algorithm to distinguish between artifact and true seizure activity.


How to deal with sickness absence among primary school pupils? Adaptation of the "Medical Advice for Sick-reported Students" intervention.
Missing school impacts both education and health. The purpose of this study was to address sickness absence in primary schools by adjusting the 'Medical Advice for Sick-reported Students' intervention for secondary schools. This was necessary because of fundamental differences in relation to the children's age and in the schools' organizational structure. The intervention mapping approach steps 1 through 4 were used to adapt 'Medical Advice for Sick-reported Students' to primary schools (MASS-PS), including a literature search, stakeholder interviews, establishing a planning group and pre-testing. In step 1, a planning group was formed and a logic model of the problem was created. In step 2, a logic model of change was created. In step 3, a theoretical basis and practical strategies were determined. In step 4, practical support materials were designed, and two pre-tests of the materials were performed. Intervention mapping was successfully used to adapt MASS to primary schools. The main changes were the lowering of the threshold for extensive sickness absence, consultations between teacher and attendance coordinator, and addition of two experts. With MASS-PS, sickness absence can be addressed as a "red flag" for underlying problems.


Differential influence of inositol hexaphosphate on the expression of genes encoding TGF-β isoforms and their receptors in intestinal epithelial cells stimulated with proinflammatory agents.
Transforming growth factor β (TGF-β) is a multifunctional cytokine recognized as an important regulator of inflammatory responses. The effect of inositol hexaphosphate (IP6), a naturally occurring phytochemical, on the mRNA expression of TGF- β1, TGF-β2, TGF-β3 and TβRI, TβRII, and TβRIII receptors stimulated with bacterial lipopolysaccharides (Escherichia coli and Salmonella typhimurium) and IL-1β in intestinal cells Caco-2 for 3 and 12 h was investigated. Real-time qRT-PCR was used to validate mRNAs level of examined genes. Bacterial endotoxin promoted differential expression of TGF-βs and their receptors in a time-dependent manner. IL-1β upregulated mRNA levels of all TGF-βs and receptors at both 3 h and 12 h. IP6 elicited the opposed to LPS effect by increasing downregulated transcription of the examined genes and suppressing the expression of TGF- β1 at 12 h. IP6 counteracted the stimulatory effect of IL-1β on TGF-β1 and receptors expression by decreasing their mRNA levels. IP6 enhanced LPS- and IL-1β-stimulated mRNA expression of TGF-β2 and -β3. Based on these studies it may be concluded that IP6 present in the intestinal milieu may exert immunoregulatory effects and chemopreventive activity on colonic epithelium under inflammatory conditions or during microbe-induced infection/inflammation by modulating the expression of genes encoding TGF-βs and their receptors at transcriptional level.


[Two immigrant children with vitamin D poisoning].
The Danish National Board of Health recommends vitamin D supplement for children under two years, regardless of race or nutrition source. Danish studies have found, that 50-80% of children of Palestinian and Pakistani origin of the ages 0-16 years had vitamin D deficiency. This case report of vitamin D poisoning in two immigrant children shows, that there is a group of people, who are not aware of the correct dosage. Doctors as well as healthcare practitioners should be aware of the problem.


Hydrogen iodide-promoted reduction of beta-chlorovinamidinium salts
HI cleanly reduced chlorovinamidinium salts to the vinamidinium salt in essentially quantitative assay yield and 55-85% isolated yield following recrystallization. The reaction proceeds via protonation of the beta-carbon atom of the vinamidinium and dechlorination via the formation of I-Cl.


Creatine monohydrate supplementation and the quality of fresh pork in normal and halothane carrier pigs.
The objective of this research was to examine the impact of supplementation with creatine monohydrate (CMH) on the quality of various muscles from normal and heterozygous halothane carrier pigs. Twenty-nine crossbred pigs, 16 normal (NN) and 13 halothane carrier (Nn) genotypes, were supplemented with 0 or 25 g x pig(-1) x d(-1) of CMH for 5 d before slaughter. Supplemented pigs gained 2.26 kg more weight (P < 0.05) during 5 d of supplementation. There were trends (P < 0.10) toward higher objective marbling scores and lower cooking loss for supplemented pigs. The 45-min pH was 0.27 units higher (P < 0.05) for supplemented pigs in the semimembranosus; CMH supplementation did not influence (P > 0.05) drip loss or muscle composition. Supplementation with CMH also resulted in lower L* values in two ham muscles, semitendinosus (5.15 units) (P < 0.05) and semimembranosus (1.95 units) (P < 0.10) for Nn carcasses. Genotype had significant effects on most quality indicators, with Nn carcasses producing lower-quality lean as evidenced by less desirable subjective and objective color and higher drip losses. Genotype also affected the composition of several muscles, with the NN carcasses having more fat and less moisture.


Multilayer Transfer Printing for Pixelated, Multicolor Quantum Dot Light-Emitting Diodes.
Here, we report multilayer stacking of films of quantum dots (QDs) for the purpose of tailoring the energy band alignment between charge transport layers and light emitting layers of different color in quantum dot light-emitting diodes (QD LED) for maximum efficiency in full color operation. The performance of QD LEDs formed by transfer printing compares favorably to that of conventional devices fabricated by spin-casting. Results indicate that zinc oxide (ZnO) and titanium dioxide (TiO2) can serve effectively as electron transport layers (ETLs) for red and green/blue QD LEDs, respectively. Optimized selections for each QD layer can be assembled at high yields by transfer printing with sacrificial fluoropolymer thin films to provide low energy surfaces for release, thereby allowing shared common layers for hole injection (HIL) and hole transport (HTL), along with customized ETLs. This strategy allows cointegration of devices with heterogeneous energy band diagrams, in a parallelized scheme that offers potential for high throughput and practical use.


GABA, its receptors, and GABAergic inhibition in mouse taste buds.
Taste buds consist of at least three principal cell types that have different functions in processing gustatory signals: glial-like (type I) cells, receptor (type II) cells, and presynaptic (type III) cells. Using a combination of Ca2+ imaging, single-cell reverse transcriptase-PCR and immunostaining, we show that GABA is an inhibitory transmitter in mouse taste buds, acting on GABA(A) and GABA(B) receptors to suppress transmitter (ATP) secretion from receptor cells during taste stimulation. Specifically, receptor cells express GABA(A) receptor subunits β2, δ, and π, as well as GABA(B) receptors. In contrast, presynaptic cells express the GABA(A) β3 subunit and only occasionally GABA(B) receptors. In keeping with the distinct expression pattern of GABA receptors in presynaptic cells, we detected no GABAergic suppression of transmitter release from presynaptic cells. We suggest that GABA may serve function(s) in taste buds in addition to synaptic inhibition. Finally, we also defined the source of GABA in taste buds: GABA is synthesized by GAD65 in type I taste cells as well as by GAD67 in presynaptic (type III) taste cells and is stored in both those two cell types. We conclude that GABA is an inhibitory transmitter released during taste stimulation and possibly also during growth and differentiation of taste buds.


Affinity labeling of the active site and the reactive sulfhydryl associated with activation of rat liver phenylalanine hydroxylase.
A pterin analogue, 5-[(3-azido-6-nitrobenzylidene)amino]-2,6-diamino-4-pyrimidinone (ANBADP), was synthesized as a probe of the pterin binding site of phenylalanine hydroxylase. The photoaffinity label has been found to be a competitive inhibitor of the enzyme with respect to 6,7-dimethyltetrahydropterin, having a Ki of 8.8 +/- 1.1 microM. The irreversible labeling of phenylalanine hydroxylase by the photoaffinity label upon irradiation is both concentration and time dependent. Phenylalanine hydroxylase is covalently labeled with a stoichiometry of 0.87 +/- 0.08 mol of label/enzyme subunit. 5-Deaza-6-methyltetrahydropterin protects against inactivation and both 5-deaza-6-methyltetrahydropterin and 6-methyltetrahydropterin protect against covalent labeling, indicating that labeling occurs at the pterin binding site. Three tryptic peptides were isolated from [3H]ANBADP-photolabeled enzyme and sequenced. All peptides indicated the sequence Thr-Leu-Lys-Ala-Leu-Tyr-Lys (residues 192-198). The residues labeled with [3H]ANBADP were Lys198 and Lys194, with the majority of the radioactivity being associated with Lys198. The reactive sulfhydryl of phenylalanine hydroxylase associated with activation of the enzyme was also identified by labeling with the chromophoric label 5-(iodoacetamido)fluorescein [Parniak, M. A., & Kaufman, S. (1981) J. Biol. Chem. 256, 6876]. Labeling of the enzyme resulted in 1 mol of fluorescein bound per phenylalanine hydroxylase subunit and a concomitant activation of phenylalanine hydroxylase to 82% of the activity found with phenylalanine-activated enzyme. Tryptic and chymotryptic peptides were isolated from fluorescein-labeled enzyme and sequenced. The modified residue was identified as Cys236.


Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells.
The β-galactoside-binding protein galectin-9 is critical in regulating the immune response, but the mechanism by which it functions remains unclear. We have demonstrated that galectin-9 is highly expressed by induced regulatory T cells (iTreg) and was crucial for the generation and function of iTreg cells, but not natural regulatory T (nTreg) cells. Galectin-9 expression within iTreg cells was driven by the transcription factor Smad3, forming a feed-forward loop, which further promoted Foxp3 expression. Galectin-9 increased iTreg cell stability and function by directly binding to its receptor CD44, which formed a complex with transforming growth factor-β (TGF-β) receptor I (TGF-βRI), and activated Smad3. Galectin-9 signaling was further found to regulate iTreg cell induction by dominantly acting through the CNS1 region of the Foxp3 locus. Our data suggest that exogenous galectin-9, in addition to being an effector molecule for Treg cells, acts synergistically with TGF-β to enforce iTreg cell differentiation and maintenance.


Analysis of typing methods for epidemiological surveillance of both methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains.
Sequence-based methods for typing Staphylococcus aureus, such as multilocus sequence typing (MLST) and spa typing, have increased interlaboratory reproducibility, portability, and speed in obtaining results, but pulsed-field gel electrophoresis (PFGE), remains the method of choice in many laboratories due to the extensive experience with this methodology and the large body of data accumulated using the technique. Comparisons between typing methods have been overwhelmingly based on a qualitative assessment of the overall agreement of results and the relative discriminatory indexes. In this study, we quantitatively assess the congruence of the major typing methods for S. aureus, using a diverse collection of 198 S. aureus strains previously characterized by PFGE, spa typing, MLST, and, in the case of methicillin-resistant S. aureus (MRSA), SCCmec typing in order to establish the quantitative congruence between the typing methods. The results of most typing methods agree in that MRSA and methicillin-susceptible S. aureus (MSSA) differ in terms of diversity of genetic backgrounds, with MSSA being more diverse. Our results show that spa typing has a very good predictive power over the clonal relationships defined by eBURST, while PFGE is less accurate for that purpose but nevertheless provides better typeability and discriminatory power. The combination of PFGE and spa typing provided even better results. Based on these observations, we suggest the use of the conjugation of spa typing and PFGE typing for epidemiological surveillance studies, since this combination provides the ability to infer long-term relationships while maintaining the discriminatory power and typeability needed in short-term studies.


Metabolic Pathways for S-Metolachlor Detoxification Differ Between Tolerant Corn and Multiple-Resistant Waterhemp.
Herbicide resistance in weeds can be conferred by target-site and/or non-target-site mechanisms, such as rapid metabolic detoxification. Resistance to the very-long-chain fatty acid-inhibiting herbicide, S-metolachlor, in multiple herbicide-resistant populations (CHR and SIR) of waterhemp (Amaranthus tuberculatus) is conferred by rapid metabolism compared with sensitive populations. However, enzymatic pathways for S-metolachlor metabolism in waterhemp are unknown. Enzyme assays using S-metolachlor were developed to determine the specific activities of glutathione S-transferases (GSTs) and cytochrome P450 monooxygenases (P450s) from CHR and SIR seedlings to compare with tolerant corn and sensitive waterhemp (WUS). GST activities were greater (∼2-fold) in CHR and SIR compared to WUS but much less than corn. In contrast, P450s in microsomal extracts from CHR and SIR formed O-demethylated S-metolachlor, and their NADPH-dependent specific activities were greater (>20-fold) than corn or WUS. Metabolite profiles of S-metolachlor generated via untargeted and targeted liquid chromatography-mass spectrometry from CHR and SIR differed from WUS, with greater relative abundances of O-demethylated S-metolachlor and O-demethylated S-metolachlor-glutathione conjugates formed by CHR and SIR. In summary, our results demonstrate that S-metolachlor metabolism in resistant waterhemp involves Phase I and Phase II metabolic activities acting in concert, but the initial O-demethylation reaction confers resistance.


Effectiveness of Inhaled Loxapine in Dual-Diagnosis Patients: A Case Series.
Episodes of psychotic agitation are frequent in patients with dual diagnosis, that is, in patients with concomitant psychiatric and substance use disorders. Rapid intervention is needed to treat the agitation at a mild stage to prevent the escalation to aggressive behavior. Inhaled loxapine has been demonstrated to rapidly improve symptoms of mild-to-moderate agitation in adults with psychiatric disorders (schizophrenia and bipolar disorder), but data on patients with dual diagnosis are scarce. This study is a retrospective review of data from a case series of patients with dual diagnosis, which were attended for symptoms of agitation while at the emergency room (n = 9), in the outpatient clinic (n = 4), or during hospitalization (n = 1) at 1 center in Spain. All patients received inhaled loxapine for treating the agitation episodes. Data from 14 patients with dual diagnosis were reviewed. All patients had 1 or more psychiatric disorders (schizophrenia, bipolar I disorder, drug-induced psychotic disorder, posttraumatic stress, borderline or antisocial personality disorder, depression, or anxiety) along with a variety of substance use disorders (alcohol, cocaine, cannabis, amphetamines, hypnotics and antianxiety drugs, caffeine, or street drugs). Overall, only 1 dose of inhaled loxapine (9.1 mg) was needed to calm each patient during an acute episode of agitation. Inhaled loxapine was rapid, effective, and well accepted in all dual-pathology patients presenting with acute agitation in the emergency setting. Inhaled loxapine facilitated both patient cooperation and an adequate management of his or her disease.


Chest computed tomography in children with COVID-19 respiratory infection.
Infection with COVID-19 is currently rare in children. To describe chest CT findings in children with COVID-19. We studied children at a large tertiary-care hospital in China, during the period from 28 January 2019 to 8 February 2020, who had positive reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19. We recorded findings at any chest CT performed in the included children, along with core clinical observations. We included five children from 10 months to 6 years of age (mean 3.4 years). All had had at least one CT scan after admission. Three of these five had CT abnormality on the first CT scan (at 2 days, 4 days and 9 days, respectively, after onset of symptoms) in the form of patchy ground-glass opacities; all normalised during treatment. Compared to reports in adults, we found similar but more modest lung abnormalities at CT in our small paediatric cohort.


Evaluation of the quality of endoscopically obtained esophageal biopsies in the dog.
An important premise for obtaining diagnostically relevant histology specimens is an appropriate biopsy technique. Goal of this study was to determine if biopsies of adequate quality can be obtained from the canine esophagus at the gastro-esophageal junction (GEJ) during routine upper gastrointestinal endoscopy. Over the course of one year, 58 dogs undergoing upper gastrointestinal endoscopy because of the presence of esophageal (n = 22) or gastrointestinal (n = 36) clinical signs were prospectively included. Five biopsies were repeatedly collected from the same dorsal and ventral locations of the GEJ, fixated individually in 4% neutral buffered formaldehyde, and evaluated histopathologically after standard preparation and haematoxylin and eosin staining. The presence of esophageal squamous epithelium with a basal cell layer and lamina propria mucosae in conjunction with foveolar columnar epithelium and cardiac glands, and the absence of fundic glands in one specimen, respectively, was judged as an adequately sampled biopsy. Adequately sampled biopsies were reported in 45 out of 58 dogs, with 31 samples originating from the dorsal GEJ, 36 samples originating from the ventral GEJ, and with 22 samples originating from both sites, respectively. The incidence of adequately sampled biopsies increased significantly over time (r = 0,22; p < 0,05), with these biopsies being reported significantly more often during the last 6 months compared to the first 6 months of the study (p = 0,03). Histopathological evaluation of the esophageal squamous epithelium showed fibrosis, inflammation, elongation of the stromal papillae, and increased thickness of the basal cell layers in 14 out of 58 dogs. Stromal papillae of the ventral esophageal epithelium were significantly elongated in dogs with esophageal clinical signs compared to dogs with gastrointestinal clinical signs (p = 0,03). After an initial learning phase adequate esophageal biopsies from the GEJ can be obtained in canine patients undergoing upper gastrointestinal endoscopy, and histological lesions can be found in these biopsies.


Tislelizumab plus zanubrutinib for Richter transformation: the phase 2 RT1 trial.
In patients with chronic lymphocytic leukemia, Richter transformation (RT) reflects the development of an aggressive lymphoma that is associated with poor response to chemotherapy and short survival. We initiated an international, investigator-initiated, prospective, open-label phase 2 study in which patients with RT received a combination of the PD-1 inhibitor tislelizumab plus the BTK inhibitor zanubrutinib for 12 cycles. Patients responding to treatment underwent maintenance treatment with both agents. The primary end point was overall response rate after six cycles. Of 59 enrolled patients, 48 patients received at least two cycles of treatment and comprised the analysis population according to the study protocol. The median observation time was 13.9 months, the median age was 67 (range 45-82) years. Ten patients (20.8%) had received previous RT-directed therapy. In total, 28 out of 48 patients responded to induction therapy with an overall response rate of 58.3% (95% confidence interval (CI) 43.2-72.4), including 9 (18.8%) complete reponse and 19 (39.6%) partial response, meeting the study's primary end point by rejecting the predefined null hypothesis of 40% (P = 0.008). Secondary end points included duration of response, progression-free survival and overall survival. The median duration of response was not reached, the median progression-free survival was 10.0 months (95% CI 3.8-16.3). Median overall survival was not reached with a 12-month overall survival rate of 74.7% (95% CI 58.4-91.0). The most common adverse events were infections (18.0%), gastrointestinal disorders (13.0%) and hematological toxicities (11.4%). These data suggest that combined checkpoint and BTK inhibition by tislelizumab plus zanubrutinib is an effective and well-tolerated treatment strategy for patients with RT. ClinicalTrials.gov Identifier: NCT04271956 .


Ubiquity and diversity of human-associated Demodex mites.
Demodex mites are a group of hair follicle and sebaceous gland-dwelling species. The species of these mites found on humans are arguably the animals with which we have the most intimate interactions. Yet, their prevalence and diversity have been poorly explored. Here we use a new molecular method to assess the occurrence of Demodex mites on humans. In addition, we use the 18S rRNA gene (18S rDNA) to assess the genetic diversity and evolutionary history of Demodex lineages. Within our samples, 100% of people over 18 years of age appear to host at least one Demodex species, suggesting that Demodex mites may be universal associates of adult humans. A phylogenetic analysis of 18S rDNA reveals intraspecific structure within one of the two named human-associated Demodex species, D. brevis. The D. brevis clade is geographically structured, suggesting that new lineages are likely to be discovered as humans from additional geographic regions are sampled.


Induction of lymphomas in mice by busulfan and chloramphenicol.
Busulfan causes long-lasting defects in the hematopoietic stem cells and in the immune system of mice. We designed studies to determine whether chloramphenicol further damaged the already defective hematopoietic stem cells of mice that were pretreated with busulfan, and we unexpectedly observed that mice given injections of the combination of busulfan and chloramphenicol developed lymphomas in relatively high incidence. The disease is invariably associated with splenomegaly and enlargement of the thymus. Leukocytosis with lymphoblasts in the peripheral blood occurred in some affected mice. The malignant cell is a lymphoblast of thymic origin. Thirteen of 37 mice which received both busulfan and chloramphenicol developed lymphomas. An additional five of the remaining 24 mice without proven lymphoma died and were not autopsied. Twelve of the 13 proven lymphomas developed within 280 days from the start of the experiment. Four of the 35 mice treated with busulfan alone developed lymphomas, and an additional five of the remaining 31 died but were not autopsied. Two of 41 mice treated with only chloramphenicol developed lymphomas. Of the mice treated with either busulfan or chloramphenicol alone that developed lymphomas, all did so more than 280 days from the start of the experiment. None of the control mice developed lymphoma. We conclude that both busulfan and chloramphenicol may induced lymphomas in mice that are not known to develop them spontaneously. The combination of both busulfan and chloramphenicol increased the frequency and accelerated the onset of the disease.


Evaluation of Artificial Intelligence-Based Intraoperative Guidance Tools for Phacoemulsification Cataract Surgery.
Complications that arise from phacoemulsification procedures can lead to worse visual outcomes. Real-time image processing with artificial intelligence tools can extract data to deliver surgical guidance, potentially enhancing the surgical environment. To evaluate the ability of a deep neural network to track the pupil, identify the surgical phase, and activate specific computer vision tools to aid the surgeon during phacoemulsification cataract surgery by providing visual feedback in real time. This cross-sectional study evaluated deidentified surgical videos of phacoemulsification cataract operations performed by faculty and trainee surgeons in a university-based ophthalmology department between July 1, 2020, and January 1, 2021, in a population-based cohort of patients. A region-based convolutional neural network was used to receive frames from the video source and, in real time, locate the pupil and in parallel identify the surgical phase being performed. Computer vision-based algorithms were applied according to the phase identified, providing visual feedback to the surgeon. Outcomes were area under the receiver operator characteristic curve and area under the precision-recall curve for surgical phase classification and Dice score (harmonic mean of the precision and recall [sensitivity]) for detection of the pupil boundary. Network performance was assessed as video output in frames per second. A usability survey was administered to volunteer cataract surgeons previously unfamiliar with the platform. The region-based convolutional neural network model achieved area under the receiver operating characteristic curve values of 0.996 for capsulorhexis, 0.972 for phacoemulsification, 0.997 for cortex removal, and 0.880 for idle phase recognition. The final algorithm reached a Dice score of 90.23% for pupil segmentation and a mean (SD) processing speed of 97 (34) frames per second. Among the 11 cataract surgeons surveyed, 8 (72%) were mostly or extremely likely to use the current platform during surgery for complex cataract. A computer vision approach using deep neural networks was able to pupil track, identify the surgical phase being executed, and activate surgical guidance tools. These results suggest that an artificial intelligence-based surgical guidance platform has the potential to enhance the surgeon experience in phacoemulsification cataract surgery. This proof-of-concept investigation suggests that a pipeline from a surgical microscope could be integrated with neural networks and computer vision tools to provide surgical guidance in real time.


Antiadhesive natural products against uropathogenic E. coli: What can we learn from cranberry extract?
Extracts from Cranberry fruits (Vaccinium macrocarpon) are traditionally used against urinary tract infections, mainly due to antiadhesive activity against uropathogenic E. coli (UPEC), but the exact mode of action and compounds, responsible for the activity, are unknown. i. To investigate if cranberry extract acts only by a single component or must be assessed as a multi-active-compound preparation; ii to screen isolated cranberry-related natural products under in vitro conditions to pinpoint natural products with antiadhesive effects against UPEC, followed by in silico calculations (QSAR) to predict potential antiadhesive compounds; iii. investigations by using urine samples from cranberry treated volunteers for evaluation on the bacterial transcriptome and the mannose-binding side of FimH, iv. to investigate if besides Tamm Horsfall Protein induction in the kidney, the extract acts also directly against UPEC. Antiadhesive activity of 105 compounds was determined by flow cytometric adhesion assay (UPEC UTI89 on T24 bladder cells). Urine samples from 16 volunteers treated with cranberry extract (p.o., 7 days, 900 mg/day) were used for ex vivo testing concerning influence on the bacterial transcriptome (Illumina RNA-seq) and interaction with the mannose binding domain of type-1 fimbriae. i. The antiadhesive effect of cranberry extract cannot be attributed to a single compound or to a single fraction. ii. Unglycosylated flavones and flavonols with bulky substitution of the B ring contribute to the antiadhesive activity. 3'-8″-biflavones and flavolignans (not related to cranberry fruits) were identified as potent antiadhesive compounds against UPEC. iii. QSAR yielded a model with good statistical performance and sufficient internal and external predictive ability. iv. Urine samples from male cranberry-treated volunteers indicated significant interaction with the mannose binding domain of type-1 fimbriae, which correlated with the amount of Tamm-Horsfall Protein in the test samples. v Cranberry extract did not influence the UPEC transcriptome; gene expression of bacterial adhesins (P-, S-fimbrae, curli) was not influenced by the urine samples, while a slight, but non-significant upregulation of type 1 fimbriae was observed. B-ring substituted flavones and flavonols from cranberry contribute to the antiadhesive activity against UPEC by inhibition of the FimH-mediated interaction with the host cell bladder epithelium.


Mapping temperature-sensitive mutants of vesicular stomatitis virus by RNA heteroduplex formation.
Duplex RNA molecules made by hybridization of virion and mRNA of vesicular stomatitis virus (VSV) were digested with ribonuclease and separated into five size classes, each containing the gene and the mRNA for one of the VSV proteins. Denaturation of the duplexes yielded full size mRNA lacking poly(A) tails. Utilizing duplex formation between the RNAs from VSV temperature-sensitive (ts) mutants and their revertants and subsequent RNase digestion under varying salt conditions, specific cleavages within a certain duplex were seen for representative mutants from complementation groups, III, IV and V. Specific cleavages were not seen for a group II mutant. From these results gene assignments cannot be made for group II; equivocal assignments are made for group III and clear assignments made for group IV and V. The assignment for the group V mutants, however, does not conform to expectations. Nevertheless, from these studies and other published ones, there is the suggestion that interactions may exist between the gene products of complementation groups II and V during VSV transcription and morphogenesis. These results also support the lack of transcriptional splicing for VSV mRNAs.


Ocular motility defects in patients with the Krupin valve implant.
To determine the prevalence of ocular motility defects following placement of a Krupin valve with disk and adjunctive mitomycin-C in glaucoma patients, a retrospective case series of all patients receiving a Krupin valve with disk and intraoperative mitomycin-C in a university-based referral practice was conducted. Each of the seven consecutive patients undergoing placement of a Krupin valve with disk in one eye because of uncontrolled glaucoma, developed significant primary position heterotropia or limitation of ocular rotations. One patient had significant postoperative diplopia. We conclude that the Krupin valve with disk used with intraoperative mitomycin-C can be associated with the development of ocular motility defects. The limitation of rotations appears to relate to the combined mechanisms of implant and cyst bulk and the displacement of the oculorotary muscles by the encapsulating cyst.


Summary: SNMMI Procedure Standard/EANM Practice Guideline for Estrogen Receptor Imaging of Patients with Breast Cancer Using 16α-[18F]Fluoro-17β-Estradiol PET.
The estrogen receptor (ER), a steroid hormone receptor important in female physiology, is a significant contributor to breast carcinogenesis and progression and, as such, is an important therapeutic target. Approximately 70% of breast cancers will express ER at presentation, and the determination of ER expression by tissue assay, usually by immunohistochemistry, is part of the standard of care for newly diagnosed breast cancer. ER expression is important in guiding the approach to treatment, especially with the increase in relevant systemic therapies. The ER-targeting imaging agent 16α-[18F]fluoro-17β-estradiol ([18F]FES) is approved for clinical use by regulatory agencies in France and the United States. Multiple studies suggest the advantages of [18F]FES PET in assessing tumor ER expression, the ability of both qualitative and quantitative [18F]FES PET measures to predict response to ER-targeted therapy, and the ability of [18F]FES PET to clarify equivocal staging and restaging results in patients with ER-expressing cancers. [18F]FES PET/CT may also be helpful in staging invasive lobular breast cancer and low-grade ER-expressing invasive ductal cancers and, in some cases, may be a substitute for biopsy. The Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine in June 2023 released a procedure standard/practice guideline for [18F]FES PET ER imaging of patients with breast cancer. The goal of the standard/guideline is to assist physicians in recommending, performing, interpreting, and reporting the results of [18F]FES PET studies for patients with breast cancer and to provide clinicians with the best available evidence, inform them about areas where robust evidence is lacking, and help them deliver the best possible diagnostic efficacy and study quality for their patients. Also reviewed are standardized quality control, quality assurance, and imaging procedures for [18F]FES PET. The authors emphasize the importance of precision, accuracy, repeatability, and reproducibility for both clinical management of patients and for use of [18F]FES PET in multicenter trials. A standardized imaging procedure, in combination with already published appropriate-use criteria, will help promote the use of [18F]FES PET and enhance subsequent research. This brief summary article reviews the content of the joint standard/guideline, which is available in its entirety at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=6414&navItemNumbe=10790.


Anderson localization makes adiabatic quantum optimization fail.
Understanding NP-complete problems is a central topic in computer science (NP stands for nondeterministic polynomial time). This is why adiabatic quantum optimization has attracted so much attention, as it provided a new approach to tackle NP-complete problems using a quantum computer. The efficiency of this approach is limited by small spectral gaps between the ground and excited states of the quantum computer's Hamiltonian. We show that the statistics of the gaps can be analyzed in a novel way, borrowed from the study of quantum disordered systems in statistical mechanics. It turns out that due to a phenomenon similar to Anderson localization, exponentially small gaps appear close to the end of the adiabatic algorithm for large random instances of NP-complete problems. This implies that unfortunately, adiabatic quantum optimization fails: The system gets trapped in one of the numerous local minima.


Torsional effect on the wrapping transition of a semiflexible polymer around a core as a model of nucleosome.
We investigated the effect of the torsional rigidity of a semiflexible chain on the wrapping transition around a spherical core, as a model of a nucleosome, the fundamental unit of chromatin. Through molecular dynamics simulation, we show that the torsional effect has a crucial effect on the chain wrapping around the core under the topological constraints. In particular, the torsional stress (i) induces the wrapping/unwrapping transition, and (ii) leads to a unique complex structure with an antagonistic wrapping direction which never appears without the topological constraints. We further examine the effect of the stretching stress for the nucleosome model in relation to the unique characteristic effect of the torsional stress on the manner of wrapping.


Impact of Cation Intercalation on the Electronic Structure of Ti3C2Tx MXenes in Sulfuric Acid.
Intercalation in Ti3C2Tx MXene is essential for a diverse set of applications such as water purification, desalination, electrochemical energy storage, and sensing. The interlayer spacing between the Ti3C2Tx nanosheets can be controlled by cation intercalation; however, the impact of intercalation on the Ti3C2Tx MXene chemical and electronic structures is not well understood. Herein, we characterized the electronic structure of pristine, Li-, Na-, K-, and Mg-intercalated Ti3C2Tx MXenes dispersed initially in water and 10 mM sulfuric acid (H2SO4) using X-ray absorption spectroscopy (XAS). The cation intercalation is found to dramatically influence the chemical environment of Ti atoms. The Ti oxidation of the MXene increases progressively upon intercalation of cations of larger sizes after drying in air, while interestingly a low Ti oxidation is observed for all intercalated MXenes after dispersion in diluted H2SO4. In situ XAS at the Ti L-edge was conducted during electrochemical oxidation to probe the changes in the Ti oxidation state in the presence of different cations in H2SO4 aqueous electrolyte. By applying the sensitivity of the Ti L-edge to probe the oxidation state of Ti atoms, we demonstrate that cation-intercalation and H2SO4 environment significantly alter the Ti3C2Tx surface chemistry.


Quantivine: A Visualization Approach for Large-scale Quantum Circuit Representation and Analysis.
Quantum computing is a rapidly evolving field that enables exponential speed-up over classical algorithms. At the heart of this revolutionary technology are quantum circuits, which serve as vital tools for implementing, analyzing, and optimizing quantum algorithms. Recent advancements in quantum computing and the increasing capability of quantum devices have led to the development of more complex quantum circuits. However, traditional quantum circuit diagrams suffer from scalability and readability issues, which limit the efficiency of analysis and optimization processes. In this research, we propose a novel visualization approach for large-scale quantum circuits by adopting semantic analysis to facilitate the comprehension of quantum circuits. We first exploit meta-data and semantic information extracted from the underlying code of quantum circuits to create component segmentations and pattern abstractions, allowing for easier wrangling of massive circuit diagrams. We then develop Quantivine, an interactive system for exploring and understanding quantum circuits. A series of novel circuit visualizations is designed to uncover contextual details such as qubit provenance, parallelism, and entanglement. The effectiveness of Quantivine is demonstrated through two usage scenarios of quantum circuits with up to 100 qubits and a formal user evaluation with quantum experts.


Mobilized peripheral blood progenitor cells (PBPC) in support of tandem cycles of high-dose chemotherapy (HDC).
We evaluated the efficacy, toxicity and feasibility of two cycles of high-dose chemotherapy (HDC), each supported with mobilized peripheral blood progenitor cells (PBPC). Ninety-six patients with metastatic or high-risk cancers received disease-specific HDC regimens. The first cycle consisted of cyclophosphamide 6000 mg/m2, thiotepa 500 mg/m2 and carboplatin 1200 mg/m2. Alternatively, some patients received etoposide 1800 mg/m2 substituted for thiotepa. A second cycle was planned 6-8 weeks later and consisted of mitoxantrone 60 mg/m2 with either melphalan 140 mg/m2 or thiotepa 600 mg/m2. PBPC were mobilized with either growth factor alone or cyclophosphamide followed by growth factor(s). Thirty-four of 96 enrolled patients (35%) did not receive the second cycle. The reasons were: patient refusal (15); insurance refusal (three); toxicities of cycle 1 (seven); no response to cycle 1 (four); and inadequate mobilization or poor engraftment, (five). Of the 33 patients who entered cycle 2 with measurable disease, 28 demonstrated further response after cycle 2 (including 10 who entered CR). One patient died of toxicity after each cycle. Hematologic recovery was rapid and complete in most patients. Tandem cycles of high-dose chemotherapy supported by PBPC are feasible and safe, although many patients fail to receive the second treatment. Preliminary evaluation shows evidence of further antitumor efficacy following cycle 2.


Prosthetic reduction of upper eyelid ptosis.
It is important that an ocularist be knowledgeable of the five types of anophthalmic ptosis, their causes and most effective treatment method. In earlier days ocularists had only one method of correcting this problem. With the advent of plastic material several more were invented, but none were totally effective or comfortable for the patient. This chapter describes the five types of ptoses, some simpler methods for correction with prostheses, but emphasizes a complex method initiated in the early 1950s by Lee Allen. It has been used by many other ocularists since. A description of the method and its effectiveness is discussed.


Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and Doxorubicin on MCF7 and MDA-MB-231 Cell Lines
Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA-MB-231 cells were cultured in RPMI 1640 containing 10% FBS and 100 U/ml penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI) kit were used respectively to compare the survival rate and apoptotic effects of different concentrations of doxorubicin and Arctium lappa root extract on MDA-MB-231 and MCF7 cells. Results: Arctium lappa root extract was able to reduce cell viability of the two cell lines in a dose and time dependent manner similar to doxorubicin. Flow cytometry results showed that similar to doxorubicin, Arctium Lappa root extract had a dose and time dependent apoptosis effect on both cell lines. 10μg/mL of Arctium lappa root extract and 5 μM of doxorubicin showed the highest anti-proliferative and apoptosis effect in MCF7 and MDA231 cells. Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+) cell lines represent two major breast cancer subtypes. The similar anti-proliferative and apoptotic effects of Arctium lappa root extract and doxorubicin (which is a conventional chemotherapy drug) on two different breast cancer cell lines strongly suggests its anticancer effects and further studies.


[Severe neutropenia during treatment with amoxicillin/clavulanic acid in a patient on regular hemodialysis treatment].
Beta-lactams are one of the most widely used antibiotics in respiratory diseases, both in adults and in the pediatric population. Their widespread use is also linked to the elevated tolerability and low risk of side effects that are generally not severe. We present here the case of a patient on regular haemodialysis pertaining to our Center who, after a seven-day treatment period with amoxicillin/clavulanic acid antibiotic therapy (medication originator), developed a framework of severe neutropenia (neutrophils till 10/mmc) resulting in hospitalization and the beginning of a specific diagnostic and therapeutic work-up. Our case is characterised, differently from other reports in the literature, for the onset of neutropenia after a short course of antibiotics, with a drug already used in the past without any side effects. During hospitalization, use of immunostimulant therapy led to the rapid recovery of a normal white blood cell count and resolution of severe neutropenia.


Recovering from an interruption: investigating speed-accuracy trade-offs in task resumption behavior.
Interruptions are disruptive because they take time to recover from, in the form of a resumption lag, and lead to an increase in the likelihood of errors being made. Despite an abundance of work investigating the effect of interruptions on routine task performance, little is known about whether there is a link between how quickly a task is resumed following an interruption (i.e., the duration of the postinterruption resumption lag) and the likelihood that an error is made. Two experiments are reported in which participants were interrupted by a cognitively demanding secondary mental arithmetic task while working on a routine sequential data-entry task. In Experiment 1 the time-cost of making an error on the primary task was varied between conditions. When errors were associated with a high time-cost penalty, participants made fewer errors and resumed the primary task more slowly than when errors were associated with a low time-cost penalty. In Experiment 2 participants were prohibited from resuming the primary task quickly by a 10-s system lockout period following the completion of the interrupting task. This lockout period led to a significant reduction in resumption errors because the lockout prohibited fast, inaccurate task resumptions. Taken together, our results suggest that longer resumption lags following an interruption are beneficial in terms of reducing the likelihood of errors being made. We discuss the practical implications of how systems might be designed to encourage more reflective task resumption behavior in situations where interruptions are commonplace. (PsycINFO Database Record (c) 2013 APA, all rights reserved).


[Equilibrium management].
Balance requires the modulation and integration of multiple sensory information, among which the vestibular apparatus of the inner ear plays an essential role. The management of all informations is assumed by a system whose adaptive capacities are much faster than we thought until recently, as demonstrated by the experiments carried out in human during the development of a vestibular implant designed to restore the lost function. While these adaptive capacities have the advantage of allowing all kinds of activities, they also have the disadvantage of producing various sensations, sometimes very strange. Enormous progress has been made recently in the investigation of vestibular disorders. However, given the complexity of the system, it must be admitted that many elements remain to be discovered. In the meantime, let us avoid considering the 'bizarre' phenomena that some patients report as the expression of a psychological disorder !


Regulation of carnitine palmitoyltransferase activity by malonyl-CoA in mitochondria from sheep liver, a tissue with a low capacity for fatty acid synthesis.
The characteristics of inhibition of carnitine palmitoyltransferase (CPT) I by malonyl-CoA were studied for the enzyme in mitochondria isolated from sheep liver, a tissue with a very low rate of fatty acid synthesis. Malonyl-CoA was as potent in inhibiting the sheep liver enzyme as in inhibiting the enzyme in rat liver mitochondria. CPT I in guinea-pig liver mitochondria was also similarly inhibited. The inhibition showed the same time-dependent characteristics previously established for the rat liver enzyme. Methylmalonyl-CoA was as effective an inhibitor of CPT I as malonyl-CoA in sheep liver mitochondria, but did not affect CPT I activity in mitochondria from rat or guinea-pig liver. The concentrations of malonyl-CoA required to inhibit CPT I in sheep liver mitochondria in vitro were similar to those found in freeze-clamped sheep liver samples (about 7 nmol of malonyl-CoA/g wet wt.). In sheep liver cells the content of malonyl-CoA was only one-tenth of that observed in vivo when glucose only was added to the incubation medium. Inclusion of acetate and/or insulin increased the malonyl-CoA content about 10-fold, to values similar to those observed in vivo. The rate of fatty acid synthesis in sheep liver cells was about 1% of that observed in rat liver, but was correlated with the concentrations of malonyl-CoA in the cells under various incubation conditions. These observations are discussed in relation to (i) the regulatory role of malonyl-CoA in tissues that have a low capacity for fatty acid synthesis, and (ii) the utilization by sheep liver of propionate as a gluconeogenic precursor.


Burden of Culture Confirmed Enteric Fever Cases in Karachi, Pakistan: Surveillance For Enteric Fever in Asia Project (SEAP), 2016-2019.
The Surveillance for Enteric Fever in Asia Project (SEAP) is a multicenter, multicountry study conducted in Pakistan, Nepal, and Bangladesh. The objectives of the study were to characterize disease incidence among patients with enteric fever. We report the burden of enteric fever at selected sites of Karachi, Pakistan. During September 2016 to September 2019, prospective surveillance was conducted at inpatient, outpatient, surgical departments, and laboratory networks of Aga Khan University Hospital, Kharadar General Hospital, and surgery units of National Institute of Child Health and Jinnah Postgraduate Medical Centre. Socio-demographic, clinical, and laboratory data were obtained from all suspected or confirmed enteric fever cases. Overall, 22% (2230/10 094) of patients enrolled were culture-positive for enteric fever. 94% (2093/2230) of isolates were Salmonella Typhi and 6% (137/2230) were S. Paratyphi. 15% of isolates multi-drug resistant (MDR) to first-line antibiotics and 60% were extensively drug-resistant (XDR), resistant to first-line antibiotics, fluoroquinolones and third generation cephalosporin. Enteric fever cases have increased during the last 3 years with large proportion of drug resistant S. Typhi cases. However, the burden of paratyphoid is still relatively low. Strengthening the existing surveillance system for enteric fever and antimicrobial resistance at the national level is recommended in Pakistan to inform prevention measures. While typhoid vaccination can significantly decrease the burden of typhoid and may also impact antimicrobial resistance, water, sanitation, and hygiene improvement is highly recommended to prevent the spread of enteric fever.


Clinically important factors influencing the diagnostic measurement of pleural fluid pH and glucose.
Accurate pleural fluid pH and glucose measurement is a key component in the diagnosis and management of patients with pleural effusion. Standardized methods of pleural fluid collection have not been defined. To assess the effect of common clinical factors that may distort measurement accuracy of pleural fluid pH and glucose. Ninety-two exudative pleural aspirates were collected in commercially available blood gas syringes. Samples were analyzed immediately using a blood gas analyzer. The effects of residual air, lidocaine, heparin, and delay in analysis (24 h) on pH and glucose measurement accuracy were assessed. Pleural fluid pH was significantly increased by residual air (mean +/- SD, 0.08 +/- 0.07; 95% confidence interval [CI], 0.06 to 0.09; P < 0.001) and significantly decreased by residual lidocaine (0.2 ml; mean change in pH, -0.15 +/- 0.09; 95% CI, -0.13 to -0.18; P < 0.001) and residual heparin (mean change in pH, -0.02 +/- 0.05; 95% CI, -0.01 to -0.04; P = 0.027). Pleural fluid pH was stable at room temperature for 1 hour and significantly increased at 4 (mean +/- SD, 0.03 +/- 0.07; 95% CI, 0.01 to 0.04; P = 0.003) and 24 hours (0.05 +/- 0.12; 95% CI, 0.03 to 0.08; P < 0.001). Pleural fluid glucose concentration was not clinically significantly altered by residual air, lidocaine (up to 0.4 ml), or 24-hour analysis delay. Accuracy of measured pleural pH is critically dependent on sample collection method. Residual air, lidocaine, and analysis delay significantly alter pH and may impact on clinical management. Pleural fluid glucose concentration is not significantly influenced by these factors. Protocols defining appropriate sampling and analysis methods are needed.


COL11A2 mutation associated with autosomal recessive Weissenbacher-Zweymuller syndrome: molecular and clinical overlap with otospondylomegaepiphyseal dysplasia (OSMED).
Autosomal recessive Weissenbacher-Zweymuller syndrome (WZS) is a skeletal dysplasia characterized by rhizomelic dwarfism and severe hearing loss. Mutations in the COL11A2 gene have been implicated in causing the autosomal dominant form of this syndrome as well as non-ocular Stickler syndrome and the autosomal recessive syndrome otospondylomegaepiphyseal dysplasia (OSMED). In a consanguineous Bedouin tribe living in Southern Israel, five individuals affected by autosomal recessive WZS were available for genetic analysis. Homozygosity of a mutation in the COL11A2 gene was found in all affected individuals. This finding lends molecular support to the clinical notion that autosomal recessive WZS and OSMED are a single entity.


Physical Compatibility of Cefiderocol with Selected Intravenous Drugs During Simulated Y-site Administration.
The physical compatibility of cefiderocol for injection (prepared as a diluted 2% cefiderocol solution) with potential co-administration drug products is presented. The compatibility of cefiderocol with a selection of 91 intravenous drugs was tested at clinically relevant concentrations using the admixed volume ratio 1:1. Compatibility of the mixtures was determined by visual observations, turbidity, and particulate-matter measurements. The mixtures were examined immediately after mixing, and then at 1 hour and 4 hours thereafter at room temperature. When using 0.9% sodium chloride or 5% dextrose injection for diluents, solutions of dobutamine hydrochloride, esomeprazole sodium, methylprednisolone acetate, propofol, rocuronium bromide, amiodarone hydrochloride, famotidine, labetalol hydrochloride, mycophenolate mofetil, acyclovir sodium, amphotericin B, caspofungin acetate, doxycycline, posaconazole, diphenhydramine hydrochloride, and phenytoin sodium were found to cause visible cloudiness upon mixing with 2% cefiderocol in both diluents. Solutions of lorazepam, tobramycin sulfate, and vancomycin hydrochloride were determined incompatible by examining the mixtures with the aid of a Tyndall light. These 19 drugs were clearly incompatible with cefiderocol for injection by visual examination. In addition, solutions of iron sucrose and albumin were incompatible with 2% cefiderocol based on sub-visual tests for turbidity and/or particulate matter. Based on sub-visual data, the 0.9% sodium chloride admixture of aminophylline and 2% cefiderocol was incompatible, while inconclusive results were obtained for the 0.9% sodium chloride admixtures of 2% cefiderocol with amikacin sulfate. Similarly, the 5% dextrose admixtures of either ciprofloxacin or polymyxin B sulfate with 2% cefiderocol were incompatible, whereas data for phenylephrine hydrochloride morphine sulfate, or undiluted sodium bicarbonate were inconclusive. Overall, the 2% cefiderocol solution was physically compatible with 63 of 91 drugs challenged at 1:1 volume ratio in both 0.9% sodium chloride and 5% dextrose diluents for at least 4 hours at the concentrations tested in this study.


Protective effect of a Chrysanthemum indicum containing formulation in cadmium-induced ototoxicity.
Chungshinchongyitang (CSCYT) is an herbal drug formula containing Chrysanthemum indicum and 13 other herbs used for treating auditory diseases. Irreversible hearing loss is a characteristic effect of a number of heavy metals. Cadmium (Cd(2+)) is an environmental contaminant that causes a variety of adverse effects. In the present study, we investigate the protective effects of CSCYT against Cd(2+) induced ototoxicity in vitro and ex vivo. The findings of this study show that CSCYT prevents the destruction of hair cell arrays induced by Cd(2+) in the rat organ of Corti primary explants. CSCYT inhibited cell death, release of cytochrome c and generation of reactive oxygen species induced by Cd(2+) in HEI-OC1 auditory cell line. In addition, we also demonstrated that CSCYT exerted its effect by modulating of apoptosis via the caspase-3 activation and extracellular signal-regulated kinase activation. These results are expected to improve the understanding of the pharmacological mechanism of CSCYT and aid in the development of potential therapeutic strategies against ototoxicity.


Understanding type and quality of relationships between individuals with chromosome 18 syndromes and their siblings.
Siblings of individuals with disabilities hold a pivotal and sometimes unappreciated position in the lives of their brother or sister. We sought to understand the unique challenges and opportunities in relationships between children with chromosome 18 conditions and their siblings and to identify the ways to support this relationship. Participants were recruited through the lay advocacy organization, the Chromosome 18 Registry & Research Society. Fifty-seven siblings from 36 families participated, using an investigator designed instrument, were asked to agree or disagreed with statements from four content areas (information and knowledge about the syndrome, feelings about the sibling relationship, involvement with and caregiving for their sibling, and support and advocacy). Siblings reported that they know their sibling with a disability very well and reported a wide range of emotions regarding their sibling. There was a strong sense of pride in their brother/sister's abilities, and many participants reported attempts to help others understand their brother/sister. Many siblings reported a dislike for the common assumption that their affected sibling is a burden on the family. Most participants reported feeling some degree of responsibility for their affected sibling, but many also reported that they enjoy this role. Sixty-three parents from 36 families responded to the survey. Most parents felt their typically developing children enjoyed teaching new things to their affected child as well as being a good role model for them. Most parents also felt their typically developing child was comfortable telling others about their sibling's condition. Recommendations for interventions and future research are discussed.


Impact of saturn ring particles on pioneer 11.
The particle flux measured by the meteoroid detectors on Pioneer 11 increased greatly while the spacecraft was near the rings of Saturn. The data suggest that the particles were associated with the rings and were not interplanetary meteoroids concentrated near the planet by gravitational focusing. The data also suggest that the E ring may be 1800 kilometers thick with an optical thickness greater than 10(-8).


Prevalence and factors associated with not receiving the booster dose of the COVID-19 vaccine in adults in Latin America and the Caribbean.
Booster doses have been described as effective in reducing hospitalizations and deaths from the new variants. However, its coverage is heterogeneous in Latin America and the Caribbean (LAC), one of the regions most affected by the pandemic. We aimed to assess the factors associated with not receiving a coronavirus disease 2019 (COVID-19) vaccine booster dose in adults from LAC. We analyzed a secondary database compiled by the University of Maryland and Facebook assessing the global impact of COVID-19. We included Facebook users over 18 years of age who resided in LAC and responded to the survey between February 13, 2022, and March 14, 2022. We evaluated sociodemographic characteristics, comorbidities, food, and economic insecurity, mental health, and vaccination-related practices. We calculated crude (cPR) and adjusted (aPR) prevalence ratios with their respective 95% confidence intervals (95%CI). The sample included 154,841 adults from 20 LAC countries. 33.7% (n = 46,459) reported not receiving the COVID-19 booster vaccine. Being under 75 years old, having a college, high school, pre-university, primary, or lower education, having no or 1 to 2 comorbidities, living in a town, having food insecurity, depressive symptoms, and having had COVID-19, were associated with a higher prevalence of not receiving the booster dose. In contrast, being female or non-binary and having anxiety symptoms were associated with a lower prevalence of not receiving the booster dose. Approximately three out of 10 adults surveyed in LAC reported not having received the booster vaccine. Authorities must design campaigns that promote receiving a booster dose considering the factors found.


[Research on convolutional neural network and its application on medical image].
Recent years, convolutional neural network (CNN) is a research hot spot in machine learning and has some application value in computer aided diagnosis. Firstly, this paper briefly introduces the basic principle of CNN. Secondly, it summarizes the improvement on network structure from two dimensions of model and structure optimization. In model structure, it summarizes eleven classical models about CNN in the past 60 years, and introduces its development process according to timeline. In structure optimization, the research progress is summarized from five aspects (input layer, convolution layer, down-sampling layer, full-connected layer and the whole network) of CNN. Thirdly, the learning algorithm is summarized from the optimization algorithm and fusion algorithm. In optimization algorithm, it combs the progress of the algorithm according to optimization purpose. In algorithm fusion, the improvement is summarized from five angles: input layer, convolution layer, down-sampling layer, full-connected layer and output layer. Finally, CNN is mapped into the medical image domain, and it is combined with computer aided diagnosis to explore its application in medical images. It is a good summary for CNN and has positive significance for the development of CNN.


International and ethnic variability of falls in older men.
Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.


Comparative Study on Interfacial Properties, Foam Stability, and Firefighting Performance of C6 Fluorocarbon Surfactants with Different Hydrophilic Groups.
Liquid fuel is flammable and hazardous, and a pool fire is one of the most serious disasters. Therefore, it is important to develop high-performance firefighting agents. To synthesize aqueous film-forming foam (AFFF) formulations, two C6 short-chain fluorocarbon surfactants Capstone 1157 (FC1157) and sodium perfluorohexylethyl sulfonate (SF852) with different hydrophilic groups were introduced, and three hydrocarbon surfactants sodium dodecyl sulfate (SDS), decyl glucoside (APG0810), and coco glucoside (APG0814) were chosen. The AFFF formulations based on the short-chain fluorocarbon-hydrocarbon compounding system were developed, and the firefighting performance of the formulations was assessed according to the standard pool fire extinction test. The results indicated that amphoteric FC1157 was slightly more effective than anionic SF852 in extinguishing small-scale pool fires and could reduce heat flux more effectively than SF852. Fluorocarbon surfactant FC1157 has been shown to suppress large pool fires much better than SF852, possibly due to its higher foam stability, higher foaming property, lower dynamic surface tension, and lower bubble coarsening rate. Both formulations we studied were more effective than commercial AFFF formulations. A concentration of 0.1-0.3% of FC1157 in an AFFF solution was optimal for extinguishing high-boiling-point oil fires.