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1.
JDS Commun ; 5(5): 368-373, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39310822

ABSTRACT

The increase in periods of heat waves leads to an increase in heat stress events in dairy cattle leading to welfare issues, production losses, and health issues. However, the low frequency of milk recording data makes genetic evaluation for heat tolerance still a challenge. A possible solution could be to add behavior data captured through sensors which are recorded permanently, mostly reported on a daily basis. The objective of this study was to evaluate the potential gain of adding behavior traits as proxies for genetic evaluation of heat tolerance. Behavior traits including activity time (ACT), rumination time (RUM), and eating time (EAT) were recorded for 453 Holstein cows equipped with SenseHub (Allflex Livestock Intelligence) collars from October 2019 to July 2022 in 6 herd located in the Walloon Region of Belgium. A multitrait reaction norm model based on separate temperature and humidity index (THI) thresholds was used. Results showed that behavior traits present not only interesting characteristics for genetic evaluation of heat tolerance but also for heat stress detection in farms. Indeed, sensors allow recording of behavior for all events of heat stress in lactating and nonlactating animals. Moderate heritability values were also found for the behavior traits (0.14 for ACT, 0.19 for RUM, and 0.12 for EAT), and a high ratio between the general and thermotolerance additive genetic variances was obtained. In addition, positive correlations of thermotolerance for ACT and EAT with thermotolerance for milk production (fat- and protein-corrected milk: 0.45 and 0.28, respectively) and negative genetic correlations of thermotolerance for ACT with somatic cells (somatic cell score: -0.39) were estimated. The genetic correlation matrix allows us to explain a high part of the variation for the reaction to heat stress of 2 economic traits (fat- and protein-corrected milk: 59% and somatic cell score: 31%) based on behavior data. Based on these results, behavior traits could be used to assess heat stress in nonlactating cattle for which the number of genetic evaluations for heat tolerance is still limited.

2.
bioRxiv ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39282294

ABSTRACT

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC. IFN-γ enhances HLA-E and PD-L1 expression in recurrent tumors, with an enrichment of intra-tumoral NKG2A-expressing NK and CD8 T cells. CXCL9+ macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7+ HLA-EHIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

3.
J Frailty Aging ; 13(3): 254-258, 2024.
Article in English | MEDLINE | ID: mdl-39082770

ABSTRACT

More than half of older adults are frail or prefrail in the United States, and hospital-associated deconditioning likely increases this risk. However, the impact of frailty on potential functional improvements after hospital discharge is poorly understood. We sought to identify the influence of baseline frailty on gait speed change in older adults receiving home health physical therapy (PT) after hospital discharge. The severity of frailty was assessed using Cardiovascular Health Study frailty criteria (weakness, slowness, weight loss, physical inactivity, and exhaustion). Gait speed was measured at baseline and 60-days post-hospital discharge. Upon admission to home health rehabilitation services, half of older adults (total N=250) were considered frail, with slowness (90%) and weakness (75%) being the most common characteristics. Older adults, whether pre-frail or frail, demonstrated similar and clinically meaningful improvements in gait speed after receiving home health rehabilitation for 60 days following hospital discharge. These results suggest that clinicians caring for older adults in the hospital can counsel both pre-frail and frail patients that, with home health rehabilitation, clinically significant improvements in function can be expected over the 2 months following discharge. Furthermore, we observed encouraging gait speed improvement with physical therapy following hospitalization in older adults. Results can inform anticipatory guidance on hospital discharge.


Subject(s)
Frail Elderly , Frailty , Home Care Services , Patient Discharge , Walking Speed , Humans , Patient Discharge/statistics & numerical data , Male , Female , Aged , Aged, 80 and over , Frailty/rehabilitation , Geriatric Assessment/methods , Physical Therapy Modalities
4.
Cogent Gerontol ; 3(1)2024.
Article in English | MEDLINE | ID: mdl-39035459

ABSTRACT

Less than half of U.S. veterans meet physical activity guidelines. Even though changing physical activity can be challenging, prior studies have demonstrated that it is possible. Older adults are using technology to aid in such behavior change. However, research that explores the mechanisms of how technology can aid in behavior change is lacking, especially among older veterans. Thus, the purpose of this secondary, convergent mixed methods study was to explore how older veterans engaged with technologies that were used during a multicomponent telerehabilitation program. The study included veterans aged ≥60 years with ≥3 chronic medical conditions and physical function limitation. Quantitative data were collected during the primary randomized controlled trial, and qualitative data were collected via individual interviews following completion of the telerehabilitation program. Data were merged and then analyzed by high vs. low technology engagement groups. Key similarities and differences between groups were identified in five domains: satisfaction with the virtual environment, coping self-efficacy, perceptions of Annie (automated text messaging platform), experiences using the activity monitor, and self-management skills. Findings can help inform the successful integration of similar technologies into physical rehabilitation programs. Further study is warranted to understand additional factors and mechanisms that influence technology engagement in telerehabilitation.

5.
Int J Tuberc Lung Dis ; 28(6): 287-294, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822484

ABSTRACT

BACKGROUNDGiven the high prevalence of asthma-chronic obstructive pulmonary disease overlap (ACO) in Vietnam, there is an urgent need to establish a simplified strategy for categorising patients as either having asthma or chronic obstructive pulmonary disease (COPD). This classification would streamline the application of treatment recommendations outlined by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).METHODSPatients with obstructive lung function were classified as having COPD, asthma, or ACO based on GINA/GOLD guidelines. We hypothesised that ACO-like asthma (ACO-A) would present with positive skin prick tests (SPTs) or early onset of symptoms without a history of tuberculosis (TB), while those with ACO-like COPD (ACO-B) would exhibit negative SPTs and late onset of symptoms and/or a history of TB.RESULTSAmong 235 patients, the prevalence of asthma, ACO-A, ACO-B, and COPD was respectively 21%, 22%, 17%, and 40%. Allergic history, rhinitis, and childhood asthma were associated with ACO-A, while high cumulative smoking was correlated with ACO-B. Socio-economic and demographic parameters, medical history, clinical features, smoking habits, lung function, and para-clinical investigations significantly differed between "all asthma" (i.e., individuals with asthma combined with ACO-A) and "all COPD" (i.e., individuals with COPD combined with ACO-B).CONCLUSIONBased on SPTs, history of TB, and onset age, ACO patients may be defined as people with asthma or COPD..


Subject(s)
Asthma , Phenotype , Pulmonary Disease, Chronic Obstructive , Humans , Middle Aged , Male , Female , Prevalence , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Adult , Asthma/epidemiology , Asthma/diagnosis , Vietnam/epidemiology , Aged , Skin Tests , Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome/epidemiology , Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome/diagnosis
6.
EClinicalMedicine ; 72: 102621, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38726222

ABSTRACT

Background: Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. Methods: We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Findings: Eleven clinical trials enrolling 5450 UC patients (infliximab = 2, adalimumab = 2, golimumab = 2, vedolizumab = 2, tofacitinib = 3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p = 0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p = 0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p = 0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p = 0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p = 0.026) in patients with extensive colitis compared to left sided. Interpretation: These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. Funding: This study did not receive any financial support.

7.
Clin Gastroenterol Hepatol ; 22(6): 1190-1199.e15, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38185396

ABSTRACT

BACKGROUND & AIMS: We conducted a network meta-analysis to compare the efficacy of advanced therapies for achieving endoscopic outcomes in patients with moderate-to-severely active Crohn's disease. METHODS: MEDLINE, Embase, and Cochrane CENTRAL databases were searched from inception to August 2, 2023 to identify phase II and III randomized controlled trials (RCTs) in adults (≥18 years) with moderate-to-severe Crohn's disease treated with tumor necrosis factor (TNF) antagonists, etrolizumab, vedolizumab, anti-interleukin (IL)12/23p40, anti-IL23p19, or Janus kinase-1 (JAK1) inhibitors, compared with placebo/active comparator, for induction and/or maintenance of remission and reported endoscopic outcomes. Primary outcome was endoscopic response after induction therapy, and endoscopic remission after maintenance therapy. We performed a random-effects network meta-analysis using a frequentist approach, and estimated relative risk (RRs), 95% confidence interval (CI) values, and P score for ranking agents. We used GRADE to ascertain certainty of evidence. RESULTS: A total of 20 RCTs (19 placebo-controlled and 1 head-to-head trial; 5592 patients) were included out of which 12 RCTs reported endoscopic outcomes for the induction phase, 5 reported for the maintenance phase, and 3 reported for both induction and maintenance phases. JAK1 inhibitors (RR, 3·49 [95% CI, 1·48-8·26]) and anti-IL23p19 (RR, 2·30 [95% CI, 1·02-5·18]) agents were more efficacious than etrolizumab (moderate certainty of evidence), and JAK1 inhibitors (RR, 2·34 [95% CI, 1·14-4·80]) were more efficacious than anti-IL12/23p40 agents for inducing endoscopic response (moderate certainty of evidence). JAK1 inhibitors and anti-IL23p19 ranked highest for induction of endoscopic response. There was paucity of RCTs of TNF antagonists reporting endoscopic outcomes with induction therapy. On network meta-analysis of 6 RCTs, all agents except vedolizumab (RR, 1.89 [95% CI, 0.61-5.92]) were effective in maintaining endoscopic remission compared with placebo. TNF antagonists, IL12/23p40, and JAK1 inhibitors were ranked highest. CONCLUSIONS: On network meta-analysis, JAK1 inhibitors and anti-IL23p19 agents may be the most effective among non-TNF-targeting advanced therapies for inducing endoscopic response. Future head-to-head trials will further inform positioning of different therapies for the management of Crohn's disease.


Subject(s)
Crohn Disease , Network Meta-Analysis , Humans , Crohn Disease/drug therapy , Treatment Outcome , Randomized Controlled Trials as Topic , Gastrointestinal Agents/therapeutic use
8.
Inflamm Bowel Dis ; 30(4): 651-659, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-37002875

ABSTRACT

BACKGROUND: Precise estimates of placebo response rates help efficient clinical trial design. In this systematic review and meta-analysis, we assessed contemporary placebo endoscopic and histological response rates in Crohn's disease (CD) clinical trials. METHODS: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to April 2022 to identify placebo-controlled studies of pharmacological interventions for CD. Endoscopic response, remission, and mucosal healing rates for participants assigned to placebo in induction and maintenance studies were pooled using a random-effects model. Point estimates and associated 95% confidence intervals (CIs) were calculated. RESULTS: In total, 16 studies (11 induction, 3 maintenance, 2 induction and maintenance) that randomized 1646 participants to placebo were eligible. For induction trials, the pooled placebo endoscopic response, endoscopic remission, and mucosal healing rates in participants assigned to placebo were 13% (95% CI, 10-16; I2 = 14.1%; P = .14), 6% (95% CI, 3-11; I2 = 74.7%; P < .001), and 6% (95% CI, 4-9; I2 = 26.9%; P = .29), respectively. The pooled endoscopic remission rate in patients who were bio-naïve was 10% (95% CI, 4-23) compared with only 4% (95% CI, 3-7) in bio-experienced patients. For maintenance trials, the pooled endoscopic response, remission, and mucosal healing rates were 7% (95% CI, 1-31; I2 = 78.2%; P = .004), 11% (95% CI, 4-27; I2 = 70.8%; P = .06), and 7% (95% CI, 3-15; I2 = 29.7; P = .23), respectively. Only 3 trials assessed histological outcomes. CONCLUSIONS: Endoscopic placebo rates vary according to trial phase and prior biologic exposure. These contemporary data will serve to inform CD trial design, sample size calculation, and end point selection for future trials.


Subject(s)
Crohn Disease , Humans , Crohn Disease/drug therapy , Endoscopy , Remission Induction , Placebo Effect , Randomized Controlled Trials as Topic
9.
Inflamm Bowel Dis ; 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38135729

ABSTRACT

BACKGROUND: This systematic review was performed to characterize the landscape of research conducted in patients with intestinal stoma (IS) and highlight unmet needs for clinical research in Crohn's disease (CD) and IS. METHODS: We searched ClinicalTrials.gov from inception to May 25, 2022, to identify clinical trials assessing interventions in patients with an IS, as well as those with an IS and CD. Studies were grouped according to type of intervention. We excluded observational studies with no treatment arm. RESULTS: A total of 253 studies were included in the final analysis. Most studies investigated devices (n = 122 [48.2%]), or surgical procedures (n = 63 [24.9%]), followed by behavioral interventions (n = 30 [11.8%]), drugs (n = 20 [7.9%]), dietary interventions (n = 2 [0.8%]), skin care products (n = 2 0.8%]), and others (n = 14 [5.5%]). A total of 50.9% (n = 129) of studies had completed recruitment, enrolling 11 116 participants. Only 6 studies (surgery: n = 3; physiological studies: n = 2; drugs: n = 1) exclusively included patients with inflammatory bowel disease (IBD), and 16 studies commented that patients with IBD were excluded in their eligibility criteria. No study assessed efficacy of drugs in patients with CD and IS. Approximately one-quarter of studies (n = 65 of 253) included quality of life as an outcome measure. CONCLUSION: There is a paucity of research in IBD patients with IS, with the majority focusing on devices and surgical procedures. There have been no drug trials evaluating efficacy in patients with CD and IS. There is an urgent need to identify barriers to enrollment and develop eligibility and outcome measures that enable the inclusion of patients with CD with stoma into clinical trials.


We analyzed registered trials for patients with intestinal stoma with special focus on Crohn's disease patients to explore research and unmet needs. Our results indicate a scarcity of studies in this area with most studies limited to surgical procedures and devices.

10.
Med Sci Educ ; 33(5): 1033-1034, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37886299

ABSTRACT

Benefits of near-peer teaching are well-documented, but its time requirements can be prohibitive. We integrated the near-peer effect into a clinical anatomy course with weekly student-developed handouts vetted by faculty to provide an element of near-peer teaching without the burden of extra time.

11.
Am J Gastroenterol ; 118(12): 2290-2293, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37410920

ABSTRACT

INTRODUCTION: To assess the safety of early vs late biologic switch in patients with inflammatory bowel disease. METHODS: In this retrospective study, we included patients with inflammatory bowel disease who underwent biologic switch between January 2014 and July 2022 at a tertiary center. The primary outcome was any infection by 6 months. RESULTS: There was no statistically significant difference between patients who had early biologic switch (≤30 days, n = 51) and late switch (>30 days, n = 77) in either infectious or noninfectious adverse events by 6 and 12 months. DISCUSSION: Early biologic switch is safe. A prolonged washout period between 2 biologics is unnecessary.


Subject(s)
Biological Products , Inflammatory Bowel Diseases , Humans , Retrospective Studies , Canada , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/chemically induced , Biological Products/adverse effects
12.
Infect Dis Ther ; 12(6): 1465-1485, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37209297

ABSTRACT

Incidence of invasive mold infections in children, while rare, is increasing as the population of high-risk patients expands, including premature infants, pediatric patients undergoing treatment for hematological malignancies, or recipients of allogeneic hematologic stem cell transplants. The infectious agents, including Aspergillus spp., Mucorales, and other molds, are especially difficult to treat and have serious morbidity and high mortality. Clinicians must maintain a high index of suspicion for invasive mold infections in at-risk patients. Diagnosis of invasive mold infections is complicated by difficulties isolating pathogens on culture, but progress is being made in immunological and molecular diagnostic technologies. Treatment in children is challenging; no randomized controlled trials exist. There is a growing body of data on treatment, specifically on safer antifungal agents, including indications for treatment, spectrum of coverage, pharmacokinetics for different ages, and pharmacodynamic targets associated with therapeutic success. However, pediatricians must often extrapolate from adult data. In this review, we aim to harmonize the existing body of literature on invasive mold infections in children, covering epidemiology, clinical presentations, diagnostic methods, and principles of management.

13.
Front Sports Act Living ; 5: 1109494, 2023.
Article in English | MEDLINE | ID: mdl-36969962

ABSTRACT

The principal aim of the work presented here is to investigate and demonstrate that a forward tilted rowing blade would result in a more efficient and effective motion of the blade through the water that would result in a higher boat speed when an equal input power is provided. A 1:5 scaled rowing boat is used to determine the performance of rowing blades with different sizes and blade angles. This is used to validate the results of a previous study where the optimal blade angle of 15 ∘ with respect to the oar shaft was determined ( 1). The input power and speed of the rowing boat can be compared between original and modified oar blades. Measurements in a towing tank demonstrate that a modified rowing blade result in faster rowing by 0.4% at the same input power. Maintaining the same stroke rate, the improvement of the blade efficiency is compensated by using a 4-6% increased blade area to yield the same input power.

14.
Am J Gastroenterol ; 118(7): 1285-1288, 2023 07 01.
Article in English | MEDLINE | ID: mdl-36757156

ABSTRACT

INTRODUCTION: We performed a systematic review to investigate whether patients with Crohn's disease (CD) and permanent ileostomy (PI) have been included in clinical trials evaluating biologics and small molecules. METHODS: MEDLINE, Embase and Cochrane library (CENTRAL) data bases were searched from inception to May 16, 2022 for placebo controlled induction and/or maintenance randomized controlled trials assessing biologics and oral small molecules in adult patients with active CD. RESULTS: Of the 81 induction and maintenance trials assessing biologics and oral small molecules in CD, none permitted the enrollment of patients with PI. Patients with CD and PI have been universally excluded from pharmaceutical trials of biologics and small molecules to date. DISCUSSION: There is an urgent need to identify barriers to enrollment and develop eligibility and outcome measures enabling the inclusion of patients with CD and PI into clinical trials.


Subject(s)
Biological Products , Crohn Disease , Adult , Humans , Crohn Disease/drug therapy , Crohn Disease/surgery , Ileostomy , Biological Products/therapeutic use , Remission Induction
15.
Clin Pediatr (Phila) ; 62(9): 1027-1031, 2023 10.
Article in English | MEDLINE | ID: mdl-36691803

ABSTRACT

Based on in vitro susceptibilities and the concern for emergence of resistance and long-term safety, ampicillin plus gentamicin remains the recommended antibiotic regimen for early onset neonatal sepsis. Our objective was to identify potential limitations of this regimen based on clinical and pathogen characteristics while minimizing risks associated with prolonged antibiotic exposure. We identified 43 gram-negative pathogens in 42 patients. Escherichia coli (E coli) occurred in 50% and Streptococcus agalactiae in 23.8% of patient. Ampicillin resistance was common, particularly in E coli (85.7%). Mortality was 23.8%, all due to E coli. We found that E coli is the most frequent pathogen and has a high mortality particularly in neonates < 1500 g; mortality is high with the current dosing strategy when E coli is resistant to ampicillin even when sensitive to gentamicin; resistance to gentamicin remains low but seems to be increasing while resistance to third-generation cephalosporins remains very low.


Subject(s)
Neonatal Sepsis , Sepsis , Infant, Newborn , Humans , Neonatal Sepsis/drug therapy , Gentamicins/therapeutic use , Escherichia coli , Ampicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Sepsis/drug therapy
16.
Rev Mal Respir ; 40(1): 24-37, 2023 Jan.
Article in French | MEDLINE | ID: mdl-36577608

ABSTRACT

COVID-19 is a viral infection with predominant respiratory tropism. In its most severe forms, the initial viral aggression leads to acute respiratory failure due to damage secondary to an exacerbated inflammatory response provoked by the activation of innate, followed by adaptive immunity. The inflammatory response may entail respiratory distress syndrome, if not multivisceral failure and death. IL-6 receptor inhibitors (Tocilizumab and Sarilumab) have been proposed as treatments. Numerous studies have provided new information, which remains heterogeneous and difficult to interpret. This review is aimed at clarifying the potential role of IL-6 receptor inhibitors in severe forms of COVID-19.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , COVID-19/complications , SARS-CoV-2 , Interleukin-6 , Treatment Outcome , Receptors, Interleukin-6
17.
Hum Vaccin Immunother ; 18(6): 2110759, 2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36084311

ABSTRACT

Invasive meningococcal disease (IMD) imposes a significant burden on the global community due to its high case fatality rate (4-20%) and the risk of long-term sequelae for one in five survivors. An expert group meeting was held to discuss the epidemiology of IMD and immunization policies in Malaysia, Philippines, Thailand, and Vietnam. Most of these countries do not include meningococcal immunization in their routine vaccination programs, except for high-risk groups such as immunocompromised people and pilgrims. It is difficult to estimate the epidemiology of IMD in the highly diverse Asia-Pacific region, but available evidence indicate serogroup B is increasingly dominant. Disease surveillance systems differ by country. IMD is not a notifiable disease in some of them. Without an adequate surveillance system in the region, the risk and the burden of IMD might well be underestimated. With the availability of new combined meningococcal vaccines and the World Health Organization roadmap to defeat bacterial meningitis by 2030, a better understanding of the epidemiology of IMD in the Asia-Pacific region is needed.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis , Humans , Incidence , Meningococcal Infections/epidemiology , Meningococcal Infections/prevention & control , Meningococcal Infections/microbiology , Vaccination , Serogroup , Thailand
18.
Front Immunol ; 13: 911873, 2022.
Article in English | MEDLINE | ID: mdl-35967449

ABSTRACT

The ability to study cancer-immune cell communication across the whole tumor section without tissue dissociation is needed, especially for cancer immunotherapy development, which requires understanding of molecular mechanisms and discovery of more druggable targets. In this work, we assembled and evaluated an integrated experimental framework and analytical process to enable genome-wide scale discovery of ligand-receptors potentially used for cellular crosstalks, followed by targeted validation. We assessed the complementarity of four different technologies: single-cell RNA sequencing and Spatial transcriptomic (measuring over >20,000 genes), RNA In Situ Hybridization (RNAscope, measuring 4-12 genes) and Opal Polaris multiplex protein staining (4-9 proteins). To utilize the multimodal data, we implemented existing methods and also developed STRISH (Spatial TRanscriptomic In Situ Hybridization), a computational method that can automatically scan across the whole tissue section for local expression of gene (e.g. RNAscope data) and/or protein markers (e.g. Polaris data) to recapitulate an interaction landscape across the whole tissue. We evaluated the approach to discover and validate cell-cell interaction in situ through in-depth analysis of two types of cancer, basal cell carcinoma and squamous cell carcinoma, which account for over 70% of cancer cases. We showed that inference of cell-cell interactions using scRNA-seq data can misdetect or detect false positive interactions. Spatial transcriptomics still suffers from misdetecting lowly expressed ligand-receptor interactions, but reduces false discovery. RNAscope and Polaris are sensitive methods for defining the location of potential ligand receptor interactions, and the STRISH program can determine the probability that local gene co-expression reflects true cell-cell interaction. We expect that the approach described here will be widely applied to discover and validate ligand receptor interaction in different types of solid cancer tumors.


Subject(s)
Single-Cell Analysis , Transcriptome , Ligands , RNA , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods
19.
Clin Radiol ; 77(10): 743-748, 2022 10.
Article in English | MEDLINE | ID: mdl-35810024

ABSTRACT

AIM: To assess the prevalence of publication bias in the radiology literature, data-mining techniques were used to extract p-values in abstracts published in key radiology journals over the past 20 years. MATERIALS AND METHODS: A total of 34,699 abstracts published in Radiology, Investigative Radiology, European Radiology, American Journal of Roentgenology, and American Journal of Neuroradiology published between January 2000 and December 2019 were included in the analysis. Automated text mining using regular expressions was used to mine abstracts for p-values. RESULTS: The text mining algorithm detected 43,489 p-values, the majority (82.4%) of which were reported as "significant", i.e., p<0.05. There has also been an increased propensity to report more p-values over time. The distribution of p-values showed a step change at the conventional significance threshold of 0.05. The odds ratio of a "significant" p-value being reported in the abstract compared to the full text was calculated to be 2.52 (95% confidence interval 1.78-3.58; p<0.001). Taken together, these results provide strong evidence for selective reporting of significant p-values in abstracts. CONCLUSION: Statistically significant p-values are preferentially reported in radiology journal abstracts.


Subject(s)
Radiology , Humans , Publication Bias , United States
20.
JMIR Diabetes ; 7(2): e33205, 2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35436214

ABSTRACT

BACKGROUND: Individuals in need of medical care turn to crowdfunding websites to engage a "crowd" or group for financial support. In the last decade, access to insulin has decreased considerably for several reasons, including the rising cost of insulin, increasing popularity of high-deductible insurance plans, and increasing insurance premiums. Many people with diabetes are forced to ration or go without insulin, and they turn to crowdfunding websites to seek financial donations to purchase insulin needed to reduce health risks and mortality, and sustain quality of life. OBJECTIVE: This study aimed to explore crowdfunding campaign requests to purchase insulin in the United States. METHODS: In this retrospective, quantitative, and qualitative study, we coded the text of GoFundMe online crowdfunding campaigns and viral measures (shares, hearts, and comments) from February 25 to April 15, 2019. We described campaigns (N=205) and explored the factors associated with campaign success using correlations and qualitative thematic analysis. RESULTS: The majority of campaigns were initiated by middle-aged adults (age 26-64 years; 77/205, 37.6%), those with type 1 diabetes (94/205, 45.9%), and those needing funds owing to insurance coverage issues (125/205, 61.0%). The factors associated with campaign success included requests for ≤US $500 (P=.007) and higher viral measures (shares, P=.007; hearts, P<.001; comments, P=.002). The following 4 themes emerged from the campaign text: (1) desire for self-management and survival, (2) diabetes management untenable given insulin access, (3) aftermath of insulin unaffordability, and (4) privacy issues with crowdfunding. Campaign comments were both supportive (tangible, informational, and emotional) and unsupportive (questioned the need for the campaign and deemed crowdfunding inappropriate). CONCLUSIONS: Despite crowdfunding websites being used to support the purchase of insulin, campaigns raised only a fraction of the money requested. Therefore, GoFundMe campaigns are not a reliable solution to obtain funds for insulin in the United States. Applying quantitative and qualitative methods is adequate to analyze online crowdfunding for costs of medications such as insulin. However, it is critical for people with diabetes to use resources other than online crowdfunding to access and obtain insulin owing to low success rates. Clinicians should routinely assess difficulty accessing or affording insulin, and federal health care policies should support lowering the cost of insulin.

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