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  1. Coromilas EJ, Kochav S, Goldenthal I, Biviano A, Garan H, Goldbarg S, et al.
    Circ Arrhythm Electrophysiol, 2021 03;14(3):e009458.
    PMID: 33554620 DOI: 10.1161/CIRCEP.120.009458
    [Figure: see text].
  2. Earp M, Tyrer JP, Winham SJ, Lin HY, Chornokur G, Dennis J, et al.
    PLoS One, 2018;13(7):e0197561.
    PMID: 29979793 DOI: 10.1371/journal.pone.0197561
    Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.
  3. Choi T, Sarkar M, Bonham M, Brock T, Brooks IA, Diug B, et al.
    Front Med (Lausanne), 2023;10:1146832.
    PMID: 37849488 DOI: 10.3389/fmed.2023.1146832
    INTRODUCTION/BACKGROUND: Course evaluation in health education is a common practice yet few comprehensive evaluations of health education exist that measure the impact and outcomes these programs have on developing health graduate capabilities.

    AIM/OBJECTIVES: To explore how curricula contribute to health graduate capabilities and what factors contribute to the development of these capabilities.

    METHODS: Using contribution analysis evaluation, a six-step iterative process, key stakeholders in the six selected courses were engaged in an iterative theory-driven evaluation. The researchers collectively developed a postulated theory-of-change. Then evidence from existing relevant documents were extracted using documentary analysis. Collated findings were presented to academic staff, industry representatives and graduates, where additional data was sought through focus group discussions - one for each discipline. The focus group data were used to validate the theory-of-change. Data analysis was conducted iteratively, refining the theory of change from one course to the next.

    RESULTS: The complexity in teaching and learning, contributed by human, organizational and curriculum factors was highlighted. Advances in knowledge, skills, attitudes and graduate capabilities are non-linear and integrated into curriculum. Work integrated learning significantly contributes to knowledge consolidation and forming professional identities for health professional courses. Workplace culture and educators' passion impact on the quality of teaching and learning yet are rarely considered as evidence of impact.

    DISCUSSION: Capturing the episodic and contextual learning moments is important to describe success and for reflection for improvement. Evidence of impact of elements of courses on future graduate capabilities was limited with the focus of evaluation data on satisfaction.

    CONCLUSION: Contribution analysis has been a useful evaluation method to explore the complexity of the factors in learning and teaching that influence graduate capabilities in health-related courses.

  4. Csorba G, Görföl T, Wiantoro S, Kingston T, Bates PJ, Huang JC
    Zootaxa, 2015 Jun 29;3980(2):267-78.
    PMID: 26249952 DOI: 10.11646/zootaxa.3980.2.7
    To date, three species of the genus Glischropus are recognized from the Indomalayan zoogeographic region-G. bucephalus from the Indochinese subregion, G. tylopus from the Sundaic subregion (Peninsular Thailand and Malaysia, Borneo, Sumatra, Moluccas) and G. javanus, restricted to Java. The investigation of the holotype and three topotype specimens of G. batjanus supported the view that the name was previously correctly regarded as the junior subjective synonym of G. tylopus. During review of material recently collected in southwestern Sumatra, Indonesia, one specimen of a yet undescribed species of Thick-thumbed bat was identified. G. aquilus n. sp. markedly differs from its congeners by its dark brown pelage, nearly black ear and tragus, and in skull proportions. The phylogenetic analysis based on cytb sequences also supports the specific distinctness of G. aquilus n. sp. Its discovery brings the count to 88 species of bats known from Sumatra.
  5. Abu Osman NA, Spence WD, Solomonidis SE, Paul JP, Weir AM
    Med Eng Phys, 2010 Sep;32(7):760-5.
    PMID: 20678997 DOI: 10.1016/j.medengphy.2010.04.020
    The purpose of this investigation was to vary the load on the patellar tendon bar and to study the subsequent effect this has on the pattern of the pressure distribution at the stump-socket interface. Ten male subjects from the Southern General Hospital in Glasgow, UK participated in this study. Measuring systems utilising strain gauge and electrohydraulic technologies were designed, developed and constructed to enable pressure measurements to be conducted. One transducer, the patellar tendon (PT) transducer, was attached to the patellar tendon bar of the socket such that the patellar tendon bar was capable of being translated by +/-10 mm towards or away from the tendon. The results of this study showed that the position of the patellar tendon bar had no significant effect on the pressure distribution around the socket indicating that it is an unnecessary feature, which, we propose, may be eliminated during manufacture of a trans-tibial socket.
  6. Chua PY, Day AC, Lai KL, Hall N, Tan LL, Khan K, et al.
    Br J Ophthalmol, 2018 Apr;102(4):539-543.
    PMID: 28794074 DOI: 10.1136/bjophthalmol-2017-310725
    PURPOSE: To estimate the incidence, and describe the clinical features and short-term clinical outcomes of acute angle closure (AAC).

    METHODS: Patients with newly diagnosed AAC were identified prospectively over a 12-month period (November 2011 to October 2012) by active surveillance through the Scottish Ophthalmic Surveillance Unit reporting system. Data were collected at case identification and at 6 months follow-up.

    RESULTS: There were 114 cases (108 patients) reported, giving an annual incidence of 2.2 cases (95% CI 1.8 to 2.6) or 2 patients (95% CI 1.7 to 2.4) per 1 00 000 in the whole population in Scotland. Precipitating factors were identified in 40% of cases. Almost one in five cases was associated with topical dilating drops. Best-corrected visual acuity (BCVA) at presentation ranged from 6/6 to perception of light. The mean presenting intraocular pressure (IOP) was 52 mm Hg (SD 11). Almost 30% cases had a delayed presentation of 3 or more days. At 6 months follow-up, 75% had BCVA of 6/12 or better and 30% were found to have glaucoma at follow-up. Delayed presentation (≥3 days) was associated with higher rate of glaucoma at follow-up (22.6% vs 60.8%, p<0.001), worse VA (0.34 vs 0.74 LogMAR, p<0.0001) and need for more topical medication (0.52 vs 1.2, p=0.003) to control IOP.

    CONCLUSION: The incidence of AAC in Scotland is relatively low compared with the Far East countries, but in line with previous European data. Almost one in five cases were associated with pupil dilation for retinal examination.

  7. Tao S, Kichula KM, Harrison GF, Farias TDJ, Palmer WH, Leaton LA, et al.
    Immunology, 2021 Apr;162(4):389-404.
    PMID: 33283280 DOI: 10.1111/imm.13289
    Killer cell immunoglobulin-like receptors (KIRs) interact with polymorphic human leucocyte antigen (HLA) class I molecules, modulating natural killer (NK) cell functions and affecting both the susceptibility and outcome of immune-mediated diseases. The KIR locus is highly diverse in gene content, copy number and allelic polymorphism within individuals and across geographical populations. To analyse currently under-represented Asian and Pacific populations, we investigated the combinatorial diversity of KIR and HLA class I in 92 unrelated Malay and 75 Malaysian Chinese individuals from the Malay Peninsula. We identified substantial allelic and structural diversity of the KIR locus in both populations and characterized novel variations at each analysis level. The Malay population is more diverse than Malay Chinese, likely representing a unique history including admixture with immigrating populations spanning several thousand years. Characterizing the Malay population are KIR haplotypes with large structural variants present in 10% individuals, and KIR and HLA alleles previously identified in Austronesian populations. Despite the differences in ancestries, the proportion of HLA allotypes that serve as KIR ligands is similar in each population. The exception is a significantly reduced frequency of interactions of KIR2DL1 with C2+ HLA-C in the Malaysian Chinese group, caused by the low frequency of C2+ HLA. One likely implication is a greater protection from preeclampsia, a pregnancy disorder associated with KIR2DL1, which shows higher incidence in the Malay than in the Malaysian Chinese. This first complete, high-resolution, characterization of combinatorial diversity of KIR and HLA in Malaysians will form a valuable reference for future clinical and population studies.
  8. Chang AB, Toombs M, Chatfield MD, Mitchell R, Fong SM, Binks MJ, et al.
    Front Pediatr, 2021;9:781168.
    PMID: 35111703 DOI: 10.3389/fped.2021.781168
    Background: Preventing and/or reducing acute lower respiratory infections (ALRIs) in young children will lead to substantial short and long-term clinical benefits. While immunisation with pneumococcal conjugate vaccines (PCV) reduces paediatric ALRIs, its efficacy for reducing infant ALRIs following maternal immunisation has not been studied. Compared to other PCVs, the 10-valent pneumococcal-Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) is unique as it includes target antigens from two common lower airway pathogens, pneumococcal capsular polysaccharides and protein D, which is a conserved H. influenzae outer membrane lipoprotein. Aims: The primary aim of this randomised controlled trial (RCT) is to determine whether vaccinating pregnant women with PHiD-CV (compared to controls) reduces ALRIs in their infants' first year of life. Our secondary aims are to evaluate the impact of maternal PHiD-CV vaccination on different ALRI definitions and, in a subgroup, the infants' nasopharyngeal carriage of pneumococci and H. influenzae, and their immune responses to pneumococcal vaccine type serotypes and protein D. Methods: We are undertaking a parallel, multicentre, superiority RCT (1:1 allocation) at four sites across two countries (Australia, Malaysia). Healthy pregnant Australian First Nation or Malaysian women aged 17-40 years with singleton pregnancies between 27+6 and 34+6 weeks gestation are randomly assigned to receive either a single dose of PHiD-CV or usual care. Treatment allocation is concealed. Study outcome assessors are blinded to treatment arms. Our primary outcome is the rate of medically attended ALRIs by 12-months of age. Blood and nasopharyngeal swabs are collected from infants at birth, and at ages 6- and 12-months (in a subset). Our planned sample size (n = 292) provides 88% power (includes 10% anticipated loss to follow-up). Discussion: Results from this RCT potentially leads to prevention of early and recurrent ALRIs and thus preservation of lung health during the infant's vulnerable period when lung growth is maximum. The multicentre nature of our study increases the generalisability of its future findings and is complemented by assessing the microbiological and immunological outcomes in a subset of infants. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374381, identifier: ACTRN12618000150246.
  9. Page DB, Broeckx G, Jahangir CA, Verbandt S, Gupta RR, Thagaard J, et al.
    J Pathol, 2023 Aug;260(5):514-532.
    PMID: 37608771 DOI: 10.1002/path.6165
    Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.
  10. Wongwaiyut P, Karapan S, Saekong P, Francis CM, Guillén-Servent A, Senawi J, et al.
    Zootaxa, 2023 May 03;5277(3):401-442.
    PMID: 37518310 DOI: 10.11646/zootaxa.5277.3.1
    A new species of small Hipposideros in the bicolor group is described based on specimens from Thailand and Malaysia. It can be distinguished from other small Hipposideros in Southeast Asia by a combination of external, craniodental, and bacular morphology, as well as echolocation call frequency. The new species has a distinct rounded swelling on the internarial septum of the noseleaf, with a forearm length of 35.3-42.6 mm, greatest skull length of 15.94-17.90 mm, and a call frequency of maximum energy of 132.3-144.0 kHz. Although clearly different in morphology, the new species forms a sister clade with H. kunzi and H. bicolor in the phylogenetic trees based on mitochondrial DNA. In addition, this study reports echolocation and genetic data, with a confirmed record of H. einnaythu from Thailand for the first time. The new species most closely resembles H. einnaythu. However, it differs in the details of the noseleaf and craniodental morphology, and it has a genetic distance of 9.6% and 10.4% based on mitochondrial COI and ND2, respectively. It is currently documented from five localities: two in peninsular Thailand, at Hala Forest in Yala Province, and Phru To Daeng Swamp Forest in Narathiwat Province, one from peninsular Malaysia at Krau Wildlife Reserve in Pahang, and another two in Sabah, Malaysian Borneo at Gunung Kinabalu, and near Madai Caves. However, it is likely that many previous records of "H. cineraceus" from Borneo refer to this species. Most records of the species are from lowland evergreen rainforest, though one record from Sabah was at 1800m. The roosting sites for this new species are currently unknown. Future research with a combination of data such as genetics, echolocation and morphology would be necessary to further determine the species geographic distribution in Southeast Asia.
  11. Goodman KA, Ou FS, Hall NC, Bekaii-Saab T, Fruth B, Twohy E, et al.
    J Clin Oncol, 2021 09 01;39(25):2803-2815.
    PMID: 34077237 DOI: 10.1200/JCO.20.03611
    PURPOSE: To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma.

    METHODS: After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy.

    RESULTS: Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached.

    CONCLUSION: Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%.

  12. Mitchell PJ, Cooper C, Fujita M, Halbout P, Åkesson K, Costa M, et al.
    Curr Osteoporos Rep, 2019 12;17(6):510-520.
    PMID: 31734907 DOI: 10.1007/s11914-019-00544-8
    PURPOSE OF REVIEW: This review sought to describe quality improvement initiatives in fragility fracture care and prevention.

    RECENT FINDINGS: A major care gap persists throughout the world in the secondary prevention of fragility fractures. Systematic reviews have confirmed that the Fracture Liaison Service (FLS) model of care is associated with significant improvements in rates of bone mineral density testing, initiation of osteoporosis treatment and adherence with treatment for individuals who sustain fragility fractures. Further, these improvements in the processes of care resulted in significant reductions in refracture risk and lower post-fracture mortality. The primary challenge facing health systems now is to ensure that best practice is delivered effectively in the local healthcare setting. Publication of clinical standards for FLS at the organisational and patient level in combination with the establishment of national registries has provided a mechanism for FLS to benchmark and improve their performance. Major efforts are ongoing at the global, regional and national level to improve the acute care, rehabilitation and secondary prevention for individuals who sustain fragility fractures. Active participation in these initiatives has the potential to eliminate current care gaps in the coming decade.

  13. Young PJ, Al-Fares A, Aryal D, Arabi YM, Ashraf MS, Bagshaw SM, et al.
    Crit Care Resusc, 2023 Jun;25(2):106-112.
    PMID: 37876605 DOI: 10.1016/j.ccrj.2023.04.008
    BACKGROUND: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis receiving unplanned invasive mechanical ventilation in the intensive care unit (ICU) is uncertain.

    OBJECTIVE: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Sepsis trial.

    DESIGN SETTING AND PARTICIPANTS: The Mega-ROX Sepsis trial is an international randomised clinical trial that will be conducted within an overarching 40,000-patient registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We anticipate that between 10,000 and 13,000 patients with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU will be enrolled in this trial.

    MAIN OUTCOME MEASURES: The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of patients discharged home.

    RESULTS AND CONCLUSIONS: Mega-ROX Sepsis will compare the effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU. The protocol and a prespecified approach to analyses are reported here to mitigate analysis bias.

  14. Young PJ, Al-Fares A, Aryal D, Arabi YM, Ashraf MS, Bagshaw SM, et al.
    Crit Care Resusc, 2023 Mar;25(1):53-59.
    PMID: 37876994 DOI: 10.1016/j.ccrj.2023.04.011
    BACKGROUND: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain.

    OBJECTIVE: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Brains trial.

    DESIGN SETTING AND PARTICIPANTS: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU.

    MAIN OUTCOME MEASURES: The primary outcome is in-hospital all-cause mortality up to 90 d from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home.

    RESULTS AND CONCLUSIONS: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias.

    TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).

  15. Pickering BS, Hardham JM, Smith G, Weingartl ET, Dominowski PJ, Foss DL, et al.
    Vaccine, 2016 09 14;34(40):4777-86.
    PMID: 27544586 DOI: 10.1016/j.vaccine.2016.08.028
    Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family Paramyxoviridae. Nipah virus has caused outbreaks of human disease in Bangladesh, Malaysia, Singapore, India and Philippines, in addition to a large outbreak in swine in Malaysia in 1998/1999. Recently, NiV was suspected to be a causative agent of an outbreak in horses in 2014 in the Philippines, while HeV has caused multiple human and equine outbreaks in Australia since 1994. A swine vaccine able to prevent shedding of infectious virus is of veterinary and human health importance, and correlates of protection against henipavirus infection in swine need to be better understood. In the present study, three groups of animals were employed. Pigs vaccinated with adjuvanted recombinant soluble HeV G protein (sGHEV) and challenged with HeV, developed antibody levels considered to be protective prior to the challenge (titers of 320). However, activation of the cell-mediated immune response was not detected, and the animals were only partially protected against challenge with 5×10(5) PFU of HeV per animal. In the second group, cross-neutralizing antibody levels against NiV in the sGHEV vaccinated animals did not reach protective levels, and with no activation of cellular immune memory, these animals were not protected against NiV. Only pigs orally infected with 5×10(4) PFU of NiV per animal were protected against nasal challenge with 5×10(5) PFU of NiV per animal. This group of pigs developed protective antibody levels, as well as cell-mediated immune memory. Peripheral blood mononuclear cells restimulated with UV-inactivated NiV upregulated IFN-gamma, IL-10 and the CD25 activation marker on CD4(+)CD8(+) T memory helper cells and to lesser extent on CD4(-)CD8(+) T cells. In conclusion, both humoral and cellular immune responses were required for protection of swine against henipaviruses.
  16. Krishnasamy S, Lomer MCE, Marciani L, Hoad CL, Pritchard SE, Paul J, et al.
    J Nutr, 2020 Nov 19;150(11):2890-2899.
    PMID: 32805050 DOI: 10.1093/jn/nxaa191
    BACKGROUND: Whole apples produce greater satiety than processed apples, but the underlying mechanisms remain unclear.

    OBJECTIVE: Our aim was to assess the intragastric processing of apple preparations and the associated small and large bowel contents using MRI.

    METHODS: An open label, 3-way crossover, randomized, controlled trial. Eighteen healthy adults (mean ± SD age, 25 ± 4 y; BMI, 22.7 ± 3.5 kg/m2) underwent serial MRI scans on 3 occasions separated by 7 d, after consumption of isocaloric (178 kcal) portions of either whole apples, apple puree, or apple juice. Gastric emptying, small bowel water content (SBWC; primary endpoint), were measured at baseline and at 45 min intervals (0-270 min) postmeal ingestion. Fullness and satiety were also assessed at each time point. Treatment effects between groups were analyzed using ANOVA.

    RESULTS: Gastric emptying half-time (GE t50) was greater (P < 0.0001) after participants consumed whole apple (mean ± SEM), 65 (3.3) min compared with when they consumed apple puree (41 [2.8] min) or apple juice (38 [2.9] min), times that did not differ. Postprandial area under the curve (AUC) (135-270 min) SBWC was also greater for whole apples than puree (P = 0.025) and juice (P = 0.0004) but juice and puree did not differ. AUC for fullness and satiety (0-270 min) postingestion was also greater (P = 0.002 and 0.004, respectively) for whole apple compared with juice but juice and puree did not differ.

    CONCLUSIONS: Gastric emptying is slower after whole apple consumption causing a greater sensation of fullness and satiety than puree or juice in healthy adults. Whole apples increased small bowel and colonic contents during the later phase of the study which may be relevant for subsequent food consumption.This study was registered at clinicaltrials.gov as NCT03714464.

  17. Tricarico S, McNeil HC, Cleary DW, Head MG, Lim V, Yap IKS, et al.
    PMID: 28702308 DOI: 10.1186/s41479-017-0030-5
    BACKGROUND: Since 2000, the widespread adoption of pneumococcal conjugate vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited access to international financial support means some middle-income countries (MICs) are trailing in the widespread use of PCVs. We review the status of PCV implementation, and discuss any needs and gaps related to low levels of PCV implementation in MICs, with analysis of possible solutions to strengthen the PCV implementation process in MICs.

    MAIN BODY: We searched PubMed, PubMed Central, Ovid MEDLINE, and SCOPUS databases using search terms related to pneumococcal immunization, governmental health policy or programmes, and MICs. Two authors independently reviewed the full text of the references, which were assessed for eligibility using pre-defined inclusion and exclusion criteria. The search terms identified 1,165 articles and the full texts of 21 were assessed for suitability, with eight articles included in the systematic review. MICs are implementing PCVs at a slower rate than donor-funded low-income countries and wealthier developed countries. A significant difference in the uptake of PCV in lower middle-income countries (LMICs) (71%) and upper middle-income countries (UMICs) (48%) is largely due to an unsuccessful process of "graduation" of MICs from GAVI assistance, an issue that arises as countries cross the income eligibility threshold and are no longer eligible to receive the same levels of financial assistance. A lack of country-specific data on disease burden, a lack of local expertise in economic evaluation, and the cost of PCV were identified as the leading causes of the slow uptake of PCVs in MICs. Potential solutions mentioned in the reviewed papers include the use of vaccine cost-effectiveness analysis and the provision of economic evidence to strengthen decision-making, the evaluation of the burden of disease, and post-introduction surveillance to monitor vaccine impact.

    CONCLUSION: The global community needs to recognise the impediments to vaccine introduction into MICs. Improving PCV access could help decrease the incidence of pneumonia and reduce the selection pressure for pneumococcal antimicrobial resistance.

  18. Thagaard J, Broeckx G, Page DB, Jahangir CA, Verbandt S, Kos Z, et al.
    J Pathol, 2023 Aug;260(5):498-513.
    PMID: 37608772 DOI: 10.1002/path.6155
    The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
  19. Zuntini AR, Carruthers T, Maurin O, Bailey PC, Leempoel K, Brewer GE, et al.
    Nature, 2024 Apr 24.
    PMID: 38658746 DOI: 10.1038/s41586-024-07324-0
    Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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