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Background: Reducing low-value care (LVC) is crucial to improve the quality of patient care while increasing the efficient use of scarce healthcare resources. Recently, strategies to de-implement LVC have been mapped against the Expert Recommendation for Implementing Change (ERIC) compilation of strategies. However, such strategies' effectiveness across different healthcare practices has not been addressed. This overview of systematic reviews aimed to investigate the effectiveness of de-implementation initiatives and specific ERIC strategy clusters. Methods: We searched MEDLINE (Ovid), Epistemonikos.org and Scopus (Elsevier) from 1 January 2010 to 17 April 2023 and used additional search strategies to identify relevant systematic reviews (SRs). Two reviewers independently screened abstracts and full texts against a priori–defined criteria, assessed the SR quality and extracted pre-specified data. We created harvest plots to display the results. Results: Of 46 included SRs, 27 focused on drug treatments, such as antibiotics or opioids, twelve on laboratory tests or diagnostic imaging and seven on other healthcare practices. In categorising de-implementation strategies, SR authors applied different techniques: creating self-developed strategies (n = 12), focussing on specific de-implementation strategies (n = 14) and using published taxonomies (n = 12). Overall, 15 SRs provided evidence for the effectiveness of de-implementation interventions to reduce antibiotic and opioid utilisation. Reduced utilisation, albeit inconsistently significant, was documented in the use of antipsychotics and benzodiazepines, as well as in laboratory tests and diagnostic imaging. Strategies within the adapt and tailor to context, develop stakeholder interrelationships, and change infrastructure and workflow ERIC clusters led to a consistent reduction in LVC practices. Conclusion: De-implementation initiatives were effective in reducing medication usage, and inconsistent significant reductions were observed for LVC laboratory tests and imaging. Notably, de-implementation clusters such as change infrastructure and workflow and develop stakeholder interrelationships emerged as the most encouraging avenues. Additionally, we provided suggestions to enhance SR quality, emphasising adherence to guidelines for synthesising complex interventions, prioritising appropriateness of care outcomes, documenting the development process of de-implementation initiatives and ensuring consistent reporting of applied de-implementation strategies. Registration: OSF Open Science Framework 5ruzw. [ABSTRACT FROM AUTHOR]

Backgrounds: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. Methods: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25–65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. Results: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. Conclusions: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative. [ABSTRACT FROM AUTHOR]

The extensive use of antibiotics created two of the biggest hazards to global health in the twenty-first century, namely, antibiotic residues and antimicrobial-resistant (AMR) bacteria. This research seeks to scrutinize the correlation between antibiotic residues and antibiotic- resistance genes (ARGs) of Staphylococcus aureus (S. aureus). 120 raw milk samples were systematically procured from diverse sources, involving dairy farms (40), farmers' houses (20), dairy shops (40), and street vendors (20). These samples underwent thorough screening for subclinical mastitis (SCM), S. aureus counts, and antibiotic residues. Coagulase-positive S. aureus (CPSA) was isolated and quantified in 15% (18/120) of the samples. Among these isolates, 94.4% displayed resistance to penicillin, 5.6% to trimethoprim, 22.2% to gentamycin, ofloxacin, and erythromycin, while 27.8% exhibited resistance to vancomycin. PCR amplification of 23S rRNA confirmed the identity of all tested strains as S. aureus (100%), which were then found to harbor ARGs associated with β-lactams (blaZ gene), aminoglycosides (aac(&)aph (2'') gene), and vancomycin (Van A gene). Milk samples that underwent reverse-phase high-performance liquid chromatography (HPLC) revealed residues of oxytetracycline, amoxicillin, and gentamicin at rates of 8.3%, 1.7%, and 6.7%, respectively, with maximum levels exceeding the European Union Maximum Residue Limits (EU-MRL) (2010). The ARGs related to multidrug-resistant (MDR) S. aureus were identified in 40% (8/20) of milk samples contaminated with antibiotic residues. [ABSTRACT FROM AUTHOR]

The global impact of the SARS-CoV-2 pandemic has been unprecedented, posing a significant public health challenge. Chronological age has been identified as a key determinant for severe outcomes associated with SARS-CoV-2 infection. Epigenetic age acceleration has previously been observed in various diseases including human immunodeficiency virus (HIV), Cytomegalovirus (CMV), cardiovascular diseases, and cancer. However, a comprehensive review of this topic is still missing in the field. In this review, we explore and summarize the research work focusing on biological aging markers, i.e., epigenetic age and telomere attrition in COVID-19 patients. From the reviewed articles, we identified a consistent pattern of epigenetic age dysregulation and shortened telomere length, revealing the impact of COVID-19 on epigenetic aging and telomere attrition. [ABSTRACT FROM AUTHOR]

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular dysplasia is an inherited disease causing fatty replacement of heart tissue. This disease often presents as T-wave inversion in the anterior leads of the electrocardiogram (ECG) with life-threatening ventricular arrhythmias. In older patients, progressive right and left ventricular failure can develop. This is a case report of postoperative death occurring in a 59-yr-old woman with undiagnosed arrhythmogenic right ventricular dysplasia after hepatic cystectomy. The patient had T-wave inversion in the inferior ECG leads and no history of arrhythmias. During general anesthesia, cardiovascular collapse occurred in the absence of arrhythmias that was unresponsive to resuscitation.

The inactivation of the mouse high-affinity IgG Fc receptor FcgammaRI resulted in a wide range of defects in antibody Fc-dependent functions. These studies showed the primary importance of FcgammaRI in endocytosis of monomeric IgG, kinetics, and extent of phagocytosis of immune complexes, in macrophage-based ADCC, and in immune complex-dependent antigen presentation to primed T cells. In the absence of FcgammaRI, antibody responses were elevated, implying the removal of a control point by the deletion of FcgammaRI. In addition, FcR-gamma chain-deficient mice were found to express partially functional FcgammaRI. Thus, FcgammaRI is an early participant in Fc-dependent cell activation and in the development of immune responses.

It has been postulated that, during evolution of the Ig superfamily, modifications of the function of individual receptors might occur by acquisition of exons and their subsequent modification, though evidence of this is lacking. Here we have analysed the interaction of mouse IgG subclasses with high-affinity FcgammaRI (CD64) which contains three Ig-like domains and is important in innate and adaptive immunity. This analysis has identified a mechanism by which the postulated modification of newly acquired exons provides gains in function. Thus, the most widely distributed FcgammaRI allele in mice (e.g. BALB/c), bound only a single IgG subclass, IgG2a, with high affinity. However, non-obese diabetic (NOD) mice expressed a unique allele that exhibits broader specificity and, in addition to binding IgG2a, FcgammaRI-NOD bound monomeric IgG3 and bound IgG2b with high affinity, an IgG subclass not bound by FcgammaRI of other mouse strains, either as monomer or multivalent immune complexes. Analysis of mutants of FcgammaRI wherein segments of the interdomain junctions were exchanged between FcgammaRI-BALB and FcgammaRI-NOD identified these regions as having major influence in 'gain-of-function' by the NOD form of FcgammaRI. Nucleotide sequence analysis of intron/exon boundaries encoding the interdomain junctions of the FcgammaRI alleles showed these to have arisen by mutation to alter existing or create new mRNA splice donor/acceptor sites, resulting in generation of modified junctions.

Current ventilator strategies aim at maintaining an open lung and limiting both peak inspiratory pressures and tidal volumes to avoid alveolar distension. Perfluorocarbons, as well as being excellent solvents for oxygen and carbon dioxide, have the unique properties of being able to recruit dependent lung regions and improve pulmonary mechanics. Optimal ventilator strategies for partial liquid ventilation (PLV) have not yet been clearly defined. In the surfactant-depleted rabbit model, an approach involving a large tidal volume (VT) (15 ml/kg) and lung filled to FRC with perfluorocarbon (PFC) was compared with strategies involving a moderate VT (9 ml/kg) and partially filled lung (6 ml/kg), a moderate VT (9 ml/kg) and lung filled to FRC with PFC, and a large VT (15 ml/kg) and partially filled lung (6 ml/kg). PEEP was maintained at 5 cm H2O except in the moderate VT, partial-filling group, in which a PEEP of 9 cm H2O was used to maintain the rabbits for the duration of the experiment. Oxygenation was satisfactory in all groups, and peak inspiratory pressures were not significantly different. However, five of the 13 animals in the large-VT, PFC-filled lung group died of a pneumothorax prior to completion of the experiment. Of the eight animals in this group surviving the experiment, two had radiographic evidence of pneumothoraces, with an additional three animals having autopsy evidence of air leak. Of the 22 animals in the other groups, all survived with the exception of a single rabbit in the large VT, partial-filling group, which had both radiographic and autopsy evidence of air leak. We conclude that there is a significant risk of barotrauma in a PLV strategy in which a large VT is used in association with a lung filled to FRC with perfluorocarbon. Adequate gas exchange can be achieved with alternative ventilation strategies in combination with PLV.

The gene encoding a tripeptidase (pepT) of Lactococcus lactis subsp. cremoris (formerly subsp. lactis) MG1363 was cloned from a genomic library in pUC19 and subsequently sequenced. The tripeptidase of L. lactis was shown to be homologous to PepT of Salmonella typhimurium with 47.4% identity in the deduced amino acid sequences. L. lactis PepT was enzymatically active in Escherichia coli and allowed growth of a peptidase-negative leucine-auxotrophic E. coli strain by liberation of Leu from a tripeptide. Using a two-step integration-excision system, a pepT-negative mutant of L. lactis was constructed. No differences between the growth of the mutant and that of the wild-type strain in milk or in chemically defined medium with casein as the sole source of essential amino acids were observed.

The mode of action of purified aminopeptidase N from Lactococcus lactis subsp. cremoris Wg2 on a complex peptide mixture of a tryptic digest from bovine beta-casein was analyzed. The oligopeptides produced in the tryptic digest before and after aminopeptidase N treatment were identified by analysis of the N- and C-terminal amino acid sequences and amino acid compositions of the isolated peptides and by on-line liquid chromatography-mass spectrometry. Incubation of purified peptides with aminopeptidase N resulted in complete hydrolysis of many peptides, while others were only partially hydrolyzed or not hydrolyzed. The tryptic digest of beta-casein exhibits a strong bitter taste, which corresponds to the strong hydrophobicity of several peptides in the tryptic digest of beta-casein. The degradation of the "bitter" tryptic digest by aminopeptidase N resulted in a decrease of hydrophobic peptides and a drastic decrease of bitterness of the reaction mixture.

The gene specifying an endopeptidase of Lactococcus lactis, named pepO, was cloned from a genomic library of L. lactis subsp. cremoris P8-2-47 in lambda EMBL3 and was subsequently sequenced. pepO is probably the last gene of an operon encoding the binding-protein-dependent oligopeptide transport system of L. lactis. The inferred amino acid sequence of PepO showed that the lactococcal endopeptidase has a marked similarity to the mammalian neutral endopeptidase EC 3.4.24.11 (enkephalinase), whereas no obvious sequence similarity with any bacterial enzyme was found. By means of gene disruption, a pepO-negative mutant was constructed. Growth and acid production of the mutant strain in milk were not affected, indicating that the endopeptidase is not essential for growth of L. lactis in milk.

The nucleotide sequence of the pepN gene from Lactococcus lactis encoding a zinc-metallo aminopeptidase has been determined. The open reading frame of 2,538 base pairs encodes a protein with a calculated M(r) of 95,368, which agrees with the apparent M(r) of 95,000 of the gene product which was identified by polyclonal antibodies raised against the purified aminopeptidase. The amino acid sequence of the aminopeptidase of L. lactis was found to be similar to the corresponding enzymes of human, rat and mouse, with almost 30% of the residues identical. Also, a highly conserved area was identified which has similarity with the active site of thermolysin. A zinc-binding site, as well as the catalytic site for PepN, is predicted to lie within this conserved stretch. Putative promoter regions upstream of PepN were confirmed by primer extension analysis.

The localization of two aminopeptidases, an X-prolyl-dipeptidyl aminopeptidase, an endopeptidase, and a tripeptidase in Lactococcus lactis was studied. Polyclonal antibodies raised against each purified peptidase are specific and do not cross-react with other peptidases. Experiments were performed by immunoblotting after cell fractionation and by electron microscopy of immunogold-labeled peptidases. All peptidases were found to be intracellular. However, immunogold studies showed a peripheral labeling of the X-prolyl-dipeptidyl aminopeptidase, the tripeptidase, and the endopeptidase. This peripheral location was further supported by the detection of these three enzymes in cell membrane fractions in which none of the two aminopeptidases was present.

An endopeptidase has been purified to homogeneity from a crude cell extract of Lactococcus lactis subsp. cremoris Wg2 by a procedure that includes diethyl-aminoethane-Sephacel chromatography, phenyl-Sepharose chromatography, hydroxylapatite chromatography, and fast protein liquid chromatography over an anion-exchange column and a hydrophobic-interaction column. Gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated a molecular mass of the purified enzyme of 70,000 Da. The endopeptidase can degrade several oligopeptides into various tetra-, tri-, and dipeptides. The endopeptidase has no aminopeptidase, carboxypeptidase, dipeptidase, or tripeptidase activity. It is optimally active at pH 6.0 to 6.5 and in the temperature range of 30 to 38 degrees C. The enzyme is inactivated by the chemical agents 1,10-phenanthroline, ethylenedinitrilotetraacetate, beta-mercaptoethanol, and phenylmethylsulfonyl fluoride and is inhibited by Cu2+ and Zn2+. The ethylenedinitrilotetraacetate- or 1,10-phenanthroline-treated enzyme can be reactivated by Co2+. Immunoblotting with specific antibodies raised against the purified endopeptidase indicated that the enzyme is also present in other Lactococcus spp., as well as in Lactobacillus spp. and Streptococcus salivarius subsp. thermophilus.

A new optical pressure transducer system (Viggo) has been assessed and compared with a standard P10 transducer (Spectramed) using a similar 20-gauge cannula, both in vitro in terms of linearity and frequency response and in vivo using an animal model. The linearity of the transducers was comparable; the resonant frequencies were 106 Hz and 75 Hz, respectively. However, the resonant frequency of the complete Spectramed system including 150-cm tubing was 11 Hz. The frequencies at which the output amplitude error exceeded 10% of the initial amplitude for the Viggo and for P10 with and without 150-cm tubing were 32 Hz, 24 Hz and 4 Hz, respectively. The principal advantage of the new transducer is that it is sufficiently compact to be mounted directly in the cannula at the wrist, so obviating the use of connecting tubing between the transducer and the cannula.

Background: Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest types of cancer, and it will be meaningful to search for new biomarkers with prognostic value to help clinicians tailor therapeutic strategies. Methods: Here we tried to use an advanced optical imaging technique, multiphoton microscopy (MPM) combining second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging, for the label-free detection of PDAC tissues from a cohort of 149 patients. An automated image processing method was used to extract collagen features from SHG images and the Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the prognostic value of collagen signatures. Results: SHG images clearly show the different characteristics of collagen fibers in tumor microenvironment. We gained eight collagen morphological features, and a Feature-score was derived for each patient by the combination of these features using ridge regression. Statistical analyses reveal that Feature-score is an independent factor, and can predict the overall survival of PDAC patients as well as provide well risk stratification. Conclusions: SHG imaging technique can potentially be a tool for the accurate diagnosis of PDAC, and this optical biomarker (Feature-score) may help clinicians make more approximate treatment decisions. [ABSTRACT FROM AUTHOR]

Integral membrane proteins (IMPs) play central roles in cellular physiology and represent the majority of known drug targets. Single-molecule fluorescence and fluorescence resonance energy transfer (FRET) methods have recently emerged as valuable tools for investigating structure–function relationships in IMPs. This review focuses on the practical foundations required for examining polytopic IMP function using single-molecule FRET (smFRET) and provides an overview of the technical and conceptual frameworks emerging from this area of investigation. In this context, we highlight the utility of smFRET methods to reveal transient conformational states critical to IMP function and the use of smFRET data to guide structural and drug mechanism-of-action investigations. We also identify frontiers where progress is likely to be paramount to advancing the field. [ABSTRACT FROM AUTHOR]

The aim of the current study was to assess the potency of the exopolymeric substances (EPS)-secreting purple non-sulfur bacteria (PNSB) on rice plants on acidic salt-affected soil under greenhouse conditions. A two-factor experiment was conducted following a completely randomized block design. The first factor was the salinity of the irrigation, and the other factor was the application of the EPS producing PNSB (Luteovulum sphaeroides EPS18, EPS37, and EPS54), with four replicates. The result illustrated that irrigation of salt water at 3–4‰ resulted in an increase in the Na+ accumulation in soil, resulting in a lower rice grain yield by 12.9–22.2% in comparison with the 0‰ salinity case. Supplying the mixture of L. sphaeroides EPS18, EPS37, and EPS54 increased pH by 0.13, NH4+ by 2.30 mg NH4+ kg−1, and available P by 8.80 mg P kg−1, and decreased Na+ by 0.348 meq Na+ 100 g−1, resulting in improvements in N, P, and K uptake and reductions in Na uptake, in comparison with the treatment without bacteria. Thus, the treatments supplied with the mixture of L. sphaeroides EPS18, EPS37, and EPS54 resulted in greater yield by 27.7% than the control treatment. [ABSTRACT FROM AUTHOR]

Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal solution could offer a non‐invasive and user‐friendly alternative. This two‐part clinical study evaluated the safety, tolerability, pharmacokinetics (PK), and dose proportionality of a novel apomorphine hydrochloride oromucosal solution, as well as its relative bioavailability to subcutaneous apomorphine injection and apomorphine sublingual film. In part A of the study, 12 patients with PD received 2 mg oromucosal apomorphine (4% weight/volume) and 2 mg subcutaneous apomorphine in a randomized order, followed by 4 and 8 mg oromucosal apomorphine. In part B of the study, 13 patients with PD received 7 mg oromucosal apomorphine (7% weight/volume) and 30 mg sublingual apomorphine in a randomized order, followed by 14 mg oromucosal apomorphine. Washout between dose administrations in both study parts was at least 2 days. Safety, tolerability, and PK were assessed pre‐ and post‐dose. Both study parts showed that oromucosal apomorphine was generally well‐tolerated. Observed side effects were typical for apomorphine administration and included asymptomatic orthostatic hypotension, yawning, fatigue, and somnolence. Oromucosal apomorphine exposure increased with dose, although less than dose proportional. The mean (SD) maximum exposure reached with 14 mg oromucosal apomorphine was 753.0 (298.6) ng*min/mL (area under the plasma concentration–time curve from zero to infinity) and 8.0 (3.3) ng/mL (maximum plasma concentration). This was comparable to exposure reached after 2 mg subcutaneous apomorphine and approximately half of the exposure observed with 30 mg sublingual apomorphine. In summary, clinically relevant plasma concentrations could be reached in PD patients without tolerability issues. [ABSTRACT FROM AUTHOR]

Severe acute respiratory infections (SARI) are estimated to be the cause of death in about 19% of all children younger than 5 years globally. The outbreak of coronaviral disease (COVID-19) caused by SARS-CoV-2, increased considerably the burden of SARI worldwide. We used data from a vaccine effectiveness study to identify the factors associated with SARS CoV-2 infection among hospitalized SARI patients. We recruited SARI patients at 3 hospitals in Serbia from 7 April 2022–1 May 2023. We collected demographic and clinical data from patients using a structured questionnaire, and all SARI patients were tested for SARS-CoV-2 by RT-PCR. We conducted an unmatched test negative case-control study. SARS-CoV-2 infected SARI patients were considered cases, while SARS CoV-2 negative SARI patients were controls. We conducted bivariate and multivariable logistic regression analysis in order to identify variables associated with SARS-CoV-2 infection. We included 110 SARI patients: 74 were cases and 36 controls. We identified 5 factors associated with SARS-CoV-2 positivity, age (OR = 1.04; 95% CI = 1.01–1.07), having received primary COVID-19 vaccine series (OR = 0.28; 95% CI = 0.09–0.88), current smoking (OR = 8.64; 95% CI = 2.43–30.72), previous SARS CoV-2 infection (OR = 3.48; 95% CI = 1.50–8.11) and number of days before seeking medical help (OR = 0.81; 95% CI = 0.64–1.02). In Serbia during a period of Omicron circulation, we found that older age, unvaccinated, hospitalized SARI patients, previously infected with SARS CoV-2 virus and those who smoked, were more likely to be SARS-CoV-2-positive; these patient populations should be prioritized for COVID vaccination. [ABSTRACT FROM AUTHOR]

Background: The magnitude of postpartum depression in Jordan during the COVID-19 pandemic is under-documented, and little is known about its potential social, demographic, and clinical correlates. This study aimed to explore the prevalence and related factors of postpartum depression among Jordanian mothers with a history of COVID-19 during pregnancy or after childbirth. Materials and Methods: This cross-sectional descriptive study was carried out in March-June 2021 among a convenient sample of 109 women with a history of COVID-19 during pregnancy or after childbirth, who were at a leading hospital equipped to care for COVID-19 cases in North Jordan. An online survey using the Edinburgh Postnatal Depression Scale (EPDS) was used to collect information from mothers with a history of COVID-19-positive tests. Results: Among the total number of women who participated in the study (n = 109), 73 women had postpartum depression. The prevalence of postpartum depression in the present study was 67%. In addition, the study found a positive statistically significant correlation between EPDS scores and being a smoker, delivery method, experiencing severe COVID-19 symptoms, and being hospitalized. Conclusions: During the COVID-19 pandemic, women had a high level of postpartum depression. It would be necessary to follow further the confirmed cases of COVID-19, and mothers should be screened for depressive symptoms during pregnancy and followed up for antenatal and postnatal care. [ABSTRACT FROM AUTHOR]

A tripeptidase from a cell extract of Lactococcus lactis subsp. cremoris Wg2 has been purified to homogeneity by DEAE-Sephacel and phenyl-Sepharose chromatography followed by gel filtration over a Sephadex G-100 SF column and a high-performance liquid chromatography TSK G3000 SW column. The enzyme appears to be a dimer with a molecular weight of between 103,000 and 105,000 and is composed of two identical subunits each with a molecular weight of about 52,000. The tripeptidase is capable of hydrolyzing only tripeptides. The enzyme activity is optimal at pH 7.5 and at 55 degrees C. EDTA inhibits the activity, and this can be reactivated with Zn, Mn, and partially with Co. The reducing agents dithiothreitol and beta-mercaptoethanol and the divalent cation Cu inhibit tripeptidase activity. Kinetic studies indicate that the peptidase hydrolyzes leucyl-leucyl-leucine with a K(m) of 0.15 mM and a V(max) of 151 mumol/min per mg of protein.

An aminopeptidase was purified to homogeneity from a crude cell extract of Lactococcus lactis subsp. cremoris Wg2 by a procedure that included diethyl-aminoethane-Sephacel chromatography, phenyl-Sepharose chromatography, gel filtration, and high-performance liquid chromatography over an anion-exchange column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single protein band with a molecular weight of 95,000. The aminopeptidase was capable of degrading several peptides by hydrolysis of the N-terminal amino acid. The peptidase had no endopeptidase or carboxypeptidase activity. The aminopeptidase activity was optimal at pH 7 and 40 degrees C. The enzyme was completely inactivated by the p-chloromecuribenzoate mersalyl, chelating agents, and the divalent cations Cu and Cd. The activity that was lost by treatment with the sulfhydryl-blocking reagents was restored with dithiothreitol or beta-mercapto-ethanol, while Zn or Co restored the activity of the 1,10-phenantroline-treated enzyme. Kinetic studies indicated that the enzyme has a relatively low affinity for lysyl-p-nitroanilide (K(m), 0.55 mM) but that it can hydrolyze this substrate at a high rate (V(max), 30 mumol/min per mg of protein).

The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic therapy docetaxel in combination with a third novel drug – daralutamide, compared with placebo on overall survival. Triple therapy with ADT, docetaxel and darolutamide resulted in improved overall survival rates as compared with ADT, docetaxel and placebo (HR 0.68; 95% CI, 0.57–0.80; p < 0.001). The side effect profile for both treatments was similar. This randomised, double blinded, placebo controlled study, was assessed to have a low risk of bias using the Cochrane Risk of Bias 2 tool. [ABSTRACT FROM AUTHOR]

The ability of myeloid cells to recognize and differentiate endogenous or exogenous ligands rely on the presence of different transmembrane protein receptors. C-type lectin receptors (CLRs), defined by the presence of a conserved structural motif called C-type lectin-like domain (CTLD), are a crucial family of receptors involved in this process, being able to recognize a diverse range of ligands from glycans to proteins or lipids and capable of initiating an immune response. The Dectin-1 and Dectin-2 clusters involve two groups of CLRs, with genes genomically linked within the natural killer cluster of genes in both humans and mice, and all characterized by the presence of a single extracellular CTLD. Fundamental immune cell functions such as antimicrobial effector mechanisms as well as internalization and presentation of antigens are induced and/or regulated through activatory, or inhibitory signalling pathways triggered by these receptors after ligand binding. In this review, we will discuss the most recent concepts regarding expression, ligands, signaling pathways and functions of each member of the Dectin clusters of CLRs, highlighting the importance and diversity of their functions., (© 2024. The Author(s).)

Electron microscopy has played a pivotal role in elucidating the ultrastructure of membrane contact sites between cellular organelles. The advent of cryo-electron microscopy has ushered in the ability to determine atomic models of constituent proteins or protein complexes within sites of membrane contact through single particle analysis. Furthermore, it enables the visualization of the three-dimensional architecture of membrane contact sites, encompassing numerous copies of proteins, whether in vitro reconstituted or directly observed in situ using cryo-electron tomography. Nevertheless, there exists a scarcity of cryo-electron microscopy studies focused on the site of membrane contact and their constitutive proteins. This review provides an overview of the contributions made by cryo-electron microscopy to our understanding of membrane contact sites, outlines the associated limitations, and explores prospects in this field. [ABSTRACT FROM AUTHOR]

Attenuated sporozoites provide a valuable model for exploring protective immunity against the malarial liver stage, guiding the design of highly efficient vaccines to prevent malaria infection. Liver tissue-resident CD8+ T cells (CD8+ Trm cells) are considered the host front-line defense against malaria and are crucial to developing prime-trap/target strategies for pre-erythrocytic stage vaccine immunization. However, the spatiotemporal regulatory mechanism of the generation of liver CD8+ Trm cells and their responses to sporozoite challenge, as well as the protective antigens they recognize remain largely unknown. Here, we discuss the knowledge gap regarding liver CD8+ Trm cell formation and the potential strategies to identify predominant protective antigens expressed in the exoerythrocytic stage, which is essential for highefficacy malaria subunit pre-erythrocytic vaccine designation. [ABSTRACT FROM AUTHOR]

Vaccination is the most effective strategy for preventing infectious diseases such as COVID-19. College students are important targets for COVID-19 vaccines given this population's lower intentions to be vaccinated; however, limited research has focused on international college students' vaccination status. This study explored how psychosocial factors from the Theory of Planned Behavior (TPB; attitudes, perceived behavioral control, subjective norms, and behavioral intentions) related to students' receipt of the full course of COVID-19 vaccines and their plans to receive a booster. Students were recruited via Amazon mTurk and the Office of the Registrar at a U.S. state university. We used binary logistic regression to examine associations between students' psychosocial factors and full COVID-19 vaccination status. Hierarchical multiple regression was employed to evaluate relationships between these factors and students' intentions to receive a booster. The majority of students in our sample (81% of international students and 55% of domestic students) received the complete vaccination series. Attitudes were significantly associated with all students' full vaccination status, while perceived behavioral control was significantly associated with domestic students' status. Students' intentions to receive COVID-19 vaccines were significantly correlated with their intentions to receive a booster, with international students scoring higher on booster intentions. Among the combined college student population, attitudes, intentions to receive COVID-19 vaccines, and subjective norms were significantly related to students' intentions to receive a booster. Findings support the TPB's potential utility in evidence-based interventions to enhance college students' COVID-19 vaccination rates. Implications for stakeholders and future research directions are discussed. [ABSTRACT FROM AUTHOR]

Objective: This study assessed Nipah virus (NiV) encephalitis epidemiology, clinical outcomes, and risk variables to inform treatment and prevention. Methodology: In a PubMed systematic search, 929 citations were found. After screening and eligibility, 22 studies were included. This study obtained age, gender, geographic regions, diagnostic methods, data collection methods, and bias risk. The case fatality rate (CFR) and NiV infection risk variables were evaluated by meta-analysis. Results: Southeast Asia, especially Bangladesh and Malaysia, had the most NiV cases. The major diagnostic method was blood and cerebrospinal fluid IgM and IgG antibody tests, and males predominated. Proxy respondents and matched controls were utilized for risk factor analyses when patients could not answer. The pooled CFR for NiV encephalitis was 61.0%, indicating severity. Risk factors included pigs, nighttime bats near homes, tree climbing, and male gender. Conclusion: Southeast Asian public health is plagued by NiV encephalitis. The high CFR calls for better diagnosis, treatment, and prevention. NiV's multiple risk factors must be understood for targeted therapy. Future research should fill knowledge gaps and improve NiV infection prevention. [ABSTRACT FROM AUTHOR]

In recent times, the use of chest X-ray (CXR) images in telemedicine has increased exponentially. However, the transfer of these images on an unsecured channel poses a serious threat to their authenticity and copyright protection. To address this problem, a chest X-ray image watermarking scheme (CXRmark) is presented in this paper using an online sequential reduced kernel extreme learning machine (OS-RKELM). U-Net is used to segment the lung area into the region of non-interest (RONI) and region of interest (ROI). An OS-RKELM is trained using the approximation coefficients (obtained by transforming training images using discrete wavelet transform) and the corresponding quantized coefficients. Subsequently, it is used to modulate the approximation coefficients. In order to avoid inadvertent deterioration in the ROI and to achieve high robustness, the proposed watermarking scheme uses different embedding strengths for ROI and RONI. Further, to enhance the security of the watermark, it has been encoded using the logistic chaotic map. To evaluate the performance of the proposed scheme, we experimented with a set of 461 CXR images from a publicly available repository: COVID-19 Image Data Collection. It has been demonstrated that CXRmark results in high perceptual quality of the signed CXRs and is robust to common interference. Further, the reversibility of the proposed CXRmark scheme is demonstrated by recovering the undistorted CXR image from the signed CXR. The comparison of the proposed scheme with state-of-the-art schemes shows that CXRmark outperforms its competitors in terms of imperceptibility and robustness. [ABSTRACT FROM AUTHOR]

The Nipah virus, a highly pathogenic zoonotic pathogen, has once again surfaced in the state of Kerala, India, with recent cases reported in 2023. This article delves into the epidemiological details of these cases, shedding light on the two fatalities that occurred in September 2023 and August 2023 as well as the suspected cases that have undergone testing. Nipah virus, known for its severe neurological and respiratory disease manifestations, remains a formidable health threat due to the lack of specific treatments or vaccines. The government's response to these recent cases, including mass testing and quarantine measures, is discussed, drawing lessons from past outbreaks in the region. Kerala has experienced multiple Nipah virus outbreaks since 2018, prompting a closer examination of environmental factors, such as deforestation and urbanization, which increase the risk of zoonotic transmission. This article underscores the global implications of Nipah virus resurgence in Kerala and emphasizes the importance of preparedness and vigilance in the face of emerging infectious diseases. The lessons learned from Kerala's experience with Nipah virus outbreaks provide valuable insights for public health professionals and policymakers worldwide. [ABSTRACT FROM AUTHOR]

Background: Point-of-care testing may reduce diagnostic uncertainty in case of suspicion of bacterial infection, thereby contributing to prudent antibiotic prescribing. We aimed to study variations in the use of point-of-care tests (C-reactive protein test, rapid streptococcal antigen detection test, and urine dipstick) among general practitioners (GPs) and the potential association between point-of-care testing and antibiotic prescribing in out-of-hours general practice. Methods: We conducted a population-based observational register-based study, based on patient contacts with out-of-hours general practice in the Central Denmark Region in 2014–2017. The tendency of GPs to use point-of-care testing was calculated, and the association between the use of point-of-care testing and antibiotic prescribing was evaluated with the use of binomial regression. Results: Out-of-hours general practice conducted 794,220 clinic consultations from 2014 to 2017, of which 16.1% resulted in an antibiotic prescription. The GP variation in the use of point-of-care testing was largest for C-reactive protein tests, with an observed variation (p90/p10 ratio) of 3.0; this means that the GPs in the 90th percentile used C-reactive protein tests three times as often as the GPs in the 10th percentile. The observed variation was 2.1 for rapid streptococcal antigen detection tests and 1.9 for urine dipsticks. The GPs who tended to use more point-of-care tests prescribed significantly more antibiotics than the GPs who tended to use fewer point-of-care tests. The GPs in the upper quintile of the tendency to use C-reactive protein test prescribed 22% more antibiotics than the GPs in the lowest quintile (21% for rapid streptococcal antigen detection tests and 8% for urine dipsticks). Up through the quintiles, this effect exhibited a positive linear dose–response correlation. Conclusion: The GPs varied in use of point-of-care testing. The GPs who tended to perform more point-of-care testing prescribed more antibiotics compared with the GPs who tended to perform fewer of these tests. [ABSTRACT FROM AUTHOR]

Fcγ receptors (FcγRs) are membrane-bound glycoproteins that bind to the fragment crystallizable (Fc) constant regions of IgG antibodies. Interactions between IgG immune complexes and FcγRs can initiate signal transduction that mediates important components of the immune response including activation of immune cells for clearance of opsonized pathogens or infected host cells. In humans, many studies have identified associations between FcγR gene polymorphisms and risk of infection, or progression of disease, suggesting a gene-level impact on FcγR-dependent immune responses. Rhesus macaques are an important translational model for most human health interventions, yet little is known about the breadth of rhesus macaque FcγR genetic diversity. This lack of knowledge prevents evaluation of the impact of FcγR polymorphisms on outcomes of preclinical studies performed in rhesus macaques. In this study we used long-read RNA sequencing to define the genetic diversity of FcγRs in 206 Indian-origin Rhesus macaques, Macaca mulatta. We describe the frequency of single nucleotide polymorphisms, insertions, deletions, frame-shift mutations, and isoforms. We also index the identified diversity using predicted and known rhesus macaque FcγR and Fc-FcγR structures. Future studies that define the functional significance of this genetic diversity will facilitate a better understanding of the correlation between human and macaque FcγR biology that is needed for effective translation of studies with antibody-mediated outcomes performed in rhesus macaques. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders on a disease spectrum that are characterized by the cytoplasmic mislocalization and aberrant phase transitions of prion-like RNA-binding proteins (RBPs). The common accumulation of TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), and other nuclear RBPs in detergent-insoluble aggregates in the cytoplasm of degenerating neurons in ALS/FTD is connected to nuclear pore dysfunction and other defects in the nucleocytoplasmic transport machinery. Recent advances suggest that beyond their canonical role in the nuclear import of protein cargoes, nuclear-import receptors (NIRs) can prevent and reverse aberrant phase transitions of TDP-43, FUS, and related prion-like RBPs and restore their nuclear localization and function. Here, we showcase the NIR family and how they recognize cargo, drive nuclear import, and chaperone prion-like RBPs linked to ALS/FTD. We also discuss the promise of enhancing NIR levels and developing potentiated NIR variants as therapeutic strategies for ALS/FTD and related neurodegenerative proteinopathies. [ABSTRACT FROM AUTHOR]

Designing routing schedules is a pivotal aspect of smart delivery systems. Therefore, the field has been blooming for decades, and numerous algorithms for this task have been proposed for various formulations of rich vehicle routing problems. There is, however, an important gap in the state of the art that concerns the lack of an established and widely-adopted approach toward thorough verification and validation of such algorithms in practical scenarios. We tackle this issue and propose a comprehensive validation approach that can shed more light on functional and non-functional abilities of the solvers. Additionally, we propose novel similarity metrics to measure the distance between the routing schedules that can be used in verifying the convergence abilities of randomized techniques. To reflect practical aspects of intelligent transportation systems, we introduce an algorithm for elaborating solvable benchmark instances for any vehicle routing formulation, alongside the set of quality metrics that help quantify the real-life characteristics of the delivery systems, such as their profitability. The experiments prove the flexibility of our approach through utilizing it to the NP-hard pickup and delivery problem with time windows, and present the qualitative, quantitative, and statistical analysis scenarios which help understand the capabilities of the investigated techniques. We believe that our efforts will be a step toward the more critical and consistent evaluation of emerging vehicle routing (and other) solvers, and will allow the community to easier confront them, thus ultimately focus on the most promising research avenues that are determined in the quantifiable and traceable manner. [ABSTRACT FROM AUTHOR]

Background: The substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows. Methods: This multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation. Results: Of 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%. Conclusion: In addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis. [ABSTRACT FROM AUTHOR]

Background: Patients with coronavirus disease 2019 (COVID-19) and coronary artery disease (CAD) or heart failure (HF) are more likely to have poor outcomes. This study aimed to determine the characteristics and outcomes of COVID-19 patients with CAD/HF across various institutions in the Philippines. Methods: We utilized the data from the Philippine CORONA Study and compared the outcomes of admitted COVID-19 patients with CAD/HF versus those without. The Student's t test, Mann-Whitney U test, binary logistic regression and multivariate regression analysis were utilized. Odds ratios (OR) and Kaplan-Meier curves were generated. Results: We included a total of 512 patients with COVID-19 had CAD/HF and 10,369 were without. CAD/HF was significantly associated with COVID severity, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. After adjusting for confounders, the presence of CAD/HF was still associated with death from a cardiac cause (OR 2.22, 95% CI 1.49–3.3, p < 0.01). Conclusions: The presence of CAD or HF was significantly associated with severity of COVID disease, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. [ABSTRACT FROM AUTHOR]

The advent of AlphaGo and its successors marked the beginning of a new paradigm in playing games using artificial intelligence. This was achieved by combining Monte Carlo tree search, a planning procedure, and deep learning. While the impact on the domain of games has been undeniable, it is less clear how useful similar approaches are in applications beyond games and how they need to be adapted from the original methodology. We perform a systematic literature review of peer-reviewed articles detailing the application of neural Monte Carlo tree search methods in domains other than games. Our goal is to systematically assess how such methods are structured in practice and if their success can be extended to other domains. We find applications in a variety of domains, many distinct ways of guiding the tree search using learned policy and value functions, and various training methods. Our review maps the current landscape of algorithms in the family of neural monte carlo tree search as they are applied to practical problems, which is a first step towards a more principled way of designing such algorithms for specific problems and their requirements. [ABSTRACT FROM AUTHOR]

In actual industrial applications, the defect detection performance of deep learning models mainly depends on the size and quality of training samples. However, defective samples are difficult to obtain, which greatly limits the application of deep learning-based surface defect detection methods to industrial manufacturing processes. Aiming at solving the problem of insufficient defective samples, a surface defect detection method based on Frequency shift-Convolutional Autoencoder (Fs-CAE) network and Statistical Process Control (SPC) thresholding was proposed. The Fs-CAE network was established by adding frequency shift operation on the basis of the CAE network. The loss of high-frequency information can be prevented through the Fs-CAE network, thereby lowering the interference to defect detection during image reconstruction. The incremental SPC thresholding was introduced to detect defects automatically. The proposed method only needs samples without defects for model training and does not require labels, thus reducing manual labeling time. The surface defect detection method was tested on the air rudder image sets from the image acquisition platform and data augmentation methods. The experimental results indicated that the detection performance of the method proposed in this paper was superior to other surface defect detection methods based on image reconstruction and object detection algorithms. The new method exhibits low false positive rate (FP rate, 0%), low false negative rate (FN rate, 10%), high accuracy (95.19%) and short detection time (0.35 s per image), which shows great potential in practical industrial applications. [ABSTRACT FROM AUTHOR]

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on postoperative recovery of non-small cell lung cancer (NSCLC) is need to be understood, thereby informing the optimal timing of surgical decision-making during the COVID-19 pandemic for NSCLC patients. This study reports the postoperative outcomes of surgical NSCLC patients with preoperative SARS-CoV-2 infection. Method: This single-center retrospective cohort study included 241 NSCLC patients who underwent lobectomy or sub-lobectomy between December 1, 2022 and February 14, 2023. Surgical outcomes of patients with preoperative SARSCoV-2 infection (stratified by the time from diagnosis of SARS-CoV-2 infection to surgery) were compared with those without preoperative SARS-CoV-2 infection. The primary outcomes were total postoperative complications and postoperative pulmonary complications (PPCs), the secondary outcomes included operation time, total postoperative drainage and time, length of hospital stay (LOS), 30-day and 90-day postoperative symptoms. Results: This study included 153 (63.5%) patients with preoperative SARS-CoV-2 infection and 88 (36.5%) patients without previous SARS-CoV-2 infection. In patients with a preoperative SARS-CoV-2 diagnosis, the incidence of total postoperative complications (OR, 3.00; 95% CI, 1.12–8.01; p=0.028) and PPCs (OR, 4.20; 95% CI, 1.11–15.91; p=0.035) both increased in patients infected having surgery within 2weeks compared with non-infection before surgery. However, patients who underwent lung resection more than 2weeks after SARS-CoV-2 diagnosis had a similar risk of postoperative complications and surgical outcomes with those non-infection before surgery. Conclusion: This is the first study to provide evidence regarding the optimum timing of lung resection surgery and assessing early outcomes after surgery in NSCLC patients with SARS-CoV-2 infection. Our study documents that the SARS-CoV-2 infection did not complicate surgical procedures for lung cancer, and suggest that lung surgery should be postponed at least 2weeks after SARSCoV-2 infection for NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Visceral sarcoma is a rare malignancy with a poor prognosis. However, there is no recommended prognostic staging system for the malignant disease. Method: We analyzed the data of patients diagnosed with primary soft tissue sarcoma (STS) of the abdomen and thoracic visceral organs between 2006 and 2017 at our hospital. Prognostic factors (size, tumor grade, and lymph node metastasis) were analyzed in our cohort (n=203) and the SEER validation cohort (n=5826). Results: Tumor size, grade, and lymph node metastasis were important prognostic factors for visceral sarcoma in both our and the SEER cohorts. Based on these prognostic factors, we established a new staging system for visceral sarcoma, by which patients could be stratified into clinically meaningful and non-overlapping stages in both our cohort and the SEER validation series. Moreover, the area under the curve (AUC) value of the staging system for 5-year survival was 0.84 (95% CI: 0.78–0.89) in our series and 0.80 (95% CI: 0.79–0.81) in SEER series, respectively. In addition, compared with the widely used FIGO staging system for female genital sarcoma, the visceral sarcoma staging system could more effectively and reliably stratify patients into four different prognostic groups. Conclusions: The visceral sarcoma staging system is applicable for STS of the abdomen and thoracic visceral organs and is better than the current FIGO staging system for female genital sarcoma and should be incorporated into the AJCC Cancer Staging Manual. [ABSTRACT FROM AUTHOR]

Background: Immunization against vaccine-preventable diseases such as shingles and pneumococcal disease is especially pertinent among older Canadians. However, vaccine uptake remains low. Data and methods: Data from the Canadian Health Survey on Seniors (CHSS) - 2019/2020 were used to examine receipt of shingles and pneumococcal vaccines among Canadians aged 65 and older living in the community. Multivariable logistic regression was used to identify individual predisposing, enabling and needs-related factors associated with receipt of each type of vaccination. Reasons reported for not getting vaccinated were also examined. Results: Based on the 2019/2020 CHSS, an estimated 36.3% of Canadians aged 65 and older (2.3 million people) had received the shingles vaccine, while 51.1% (3.1 million) had received the pneumococcal vaccine. Being a woman, having higher socioeconomic status, having had the flu shot and having a regular health care provider were associated with increased odds of vaccination. Being an immigrant, living outside large population centres, and belonging to South Asian or Chinese population groups were associated with lower odds of vaccination. Over one-third of unvaccinated people did not think the shingles vaccine (39.7%) or the pneumococcal vaccine (36.6%) was necessary. Other frequently reported reasons for non-vaccination were not having heard of the vaccine or the doctor not mentioning it; for the shingles vaccine, 12% cited cost as a reason. Interpretation: Understanding factors associated with uptake of vaccines and reasons for not obtaining them among older Canadians will help to inform policy and programs aimed at preventing the burden of these diseases. [ABSTRACT FROM AUTHOR]

Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer can be described as the second most common cancer worldwide in men. Systemic treatment initially with androgen deprivation therapy is the standard care for hormone-sensitive prostate cancer, aiming to reduce androgen receptors and result in tumor shrinkage. In addition, early combination treatment with androgen deprivation therapy (ADT) and novel anti-androgen agents or ADT with chemotherapy are recommended for selected patients. This umbrella review evaluated the medical treatment for hormone-sensitive prostate cancer, including ADT alone (bilateral orchiectomy, gonadotropin hormone-releasing hormone (GnRH) agonists and GnRH antagonists) or combination treatments (ADT with chemotherapy, ADT with enzalutamide, ADT with abiraterone and ADT with apalutamide). The results showed that combination treatments significantly improved OS compared with ADT alone in both OS and PFS outcomes with more adverse events, but no OS advantage of any combination regimen was observed over the others. However, high overlap of primary RCTs was found among meta-analyses. Purpose: This umbrella review focused on evaluating the efficacy and adverse events of the metastatic hormone-sensitive prostate cancer patients receiving any treatment regimens, including ADT alone or combination treatments. Methods: This study conducted an umbrella review following the PRISMA 2020 checklist, aiming to summarize the available studies to evaluate the efficacy of medical treatments for metastatic hormone-sensitive prostate cancer. A literature search was performed to identify systematic reviews and meta-analyses (SRMAs) that included only randomized controlled trials (RCTs) up to September 2023. This study summarized their findings, evaluated overlapping data (i.e., the same RCTs were included in >one SRMA), tested for excessive significance (i.e., observed number of statistically significant studies > expected number by chance) and assessed the quality of the studies. Results: A total of 4191 studies were identified, but only 27 were included. Among those 27 studies, 12 were network meta-analyses and 15 were direct meta-analyses. Most studies showed no statistically significant difference in overall mortality among GnRH agonists, antagonists and bilateral orchiectomy. Combination treatment is more beneficial than ADT alone in both OS and PFS outcomes with more adverse events. Nevertheless, there is no OS advantage of any combination regimen over the others. Conclusion: Combination treatments demonstrated clear benefits in OS and PFS over ADT alone with more AEs. Further studies are needed to compare among combination treatments. [ABSTRACT FROM AUTHOR]

Background: Falls impact over 25% of older adults annually, making fall prevention a critical public health focus. We aimed to develop and validate a machine learning-based prediction model for serious fall-related injuries (FRIs) among community-dwelling older adults, incorporating various medication factors. Methods: Utilizing annual national patient sample data, we segmented outpatient older adults without FRIs in the preceding three months into development and validation cohorts based on data from 2018 and 2019, respectively. The outcome of interest was serious FRIs, which we defined operationally as incidents necessitating an emergency department visit or hospital admission, identified by the diagnostic codes of injuries that are likely associated with falls. We developed four machine-learning models (light gradient boosting machine, Catboost, eXtreme Gradient Boosting, and Random forest), along with a logistic regression model as a reference. Results: In both cohorts, FRIs leading to hospitalization/emergency department visits occurred in approximately 2% of patients. After selecting features from initial set of 187, we retained 26, with 15 of them being medication-related. Catboost emerged as the top model, with area under the receiver operating characteristic of 0.700, along with sensitivity and specificity rates around 65%. The high-risk group showed more than threefold greater risk of FRIs than the low-risk group, and model interpretations aligned with clinical intuition. Conclusion: We developed and validated an explainable machine-learning model for predicting serious FRIs in community-dwelling older adults. With prospective validation, this model could facilitate targeted fall prevention strategies in primary care or community-pharmacy settings. [ABSTRACT FROM AUTHOR]