Challenges and perspectives in computational deconvolution of genomics data.

Deciphering cell-type heterogeneity is crucial for systematically understanding tissue homeostasis and its dysregulation in diseases. Computational deconvolution is an efficient approach for estimating cell-type abundances from a variety of omics data. Despite substantial methodological progress in computational deconvolution in recent years, challenges are still outstanding. Here we enlist four important challenges related to computational deconvolution: the quality of the reference data, generation of ground truth data, limitations of computational methodologies, and benchmarking design and implementation. Finally, we make recommendations on reference data generation, new directions of computational methodologies, and strategies to promote rigorous benchmarking.

Miniature three-photon microscopy maximized for scattered fluorescence collection.

In deep-tissue multiphoton microscopy, diffusion and scattering of fluorescent photons, rather than ballistic emanation from the focal point, have been a confounding factor. Here we report on a 2.17-g miniature three-photon microscope (m3PM) with a configuration that maximizes fluorescence collection when imaging in highly scattering regimes. We demonstrate its capability by imaging calcium activity throughout the entire cortex and dorsal hippocampal CA1, up to 1.2 mm depth, at a safe laser power. It also enables the detection of sensorimotor behavior-correlated activities of layer 6 neurons in the posterior parietal cortex in freely moving mice during single-pellet reaching tasks. Thus, m3PM-empowered imaging allows the study of neural mechanisms in deep cortex and subcortical structures, like the dorsal hippocampus and dorsal striatum, in freely behaving animals.

Textural Precursor Compositions Harvested for Independent Signal Generators: Scaling Micron-Sized Flower-Like Metal-Organic Frameworks as Amplifying Units for Dual-Mode Glycoprotein Assay.

In this work, a micron-sized flower-like metal-organic frameworks (MOFs)-based boronate-affinity sandwich-type immunoassay was fabricated for the dual-mode glycoprotein assay. For proof of concept, the flower-like MOFs were synthesized from transition Cu nodes and tetrakis (4-carboxyphenyl) porphyrin (TCPP) ligands by spontaneous standing assembly. In addition, the specificity toward glycoprotein involved the antigen recognition as well as covalent bonding via the boronate-glycan affinity, and the immediate signal responses were initiated by textural decomposition of the flower-like MOFs. Intriguingly, Cu nodes, of which the valence state is dominant by CuI species, can endow the Fenton-like catalytic reaction of the fluorogenic substrate for generating fluorescence signals. For benefits, TCPP ligands, in which each TCPP molecule has four guest donors, can provide multiple valences for the assembly of cyclodextrin-capped gold nanoparticles via host-guest interaction for colorimetry output. Albeit important, the scaling micrometer patterns for the flower-like MOFs carrying numerous Cu nodes and TCPP ligands can also function as amplifying units, signifying the output signal. The detection limit of the dual-mode glycoprotein assay can reach 10.5 nM for the fluorescence mode and 18.7 nM for the colorimetry mode, respectively. Furthermore, the merits of harvesting different signal generators toward the multimodal readout patterns can allow the mutual verification and make the analytical results more reliable. Collectively, our proposed assay may offer a new idea in combining the inherent textural merits from MOFs for dual signal generators, which can also emphasize accurate detection capability for glycoprotein assay.

Predictive factors that influence the clinical efficacy of umbilical cord-derived mesenchymal stromal cells in the treatment of type 2 diabetes mellitus.

BACKGROUND: Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint. METHODS: In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed. RESULTS: At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels. CONCLUSIONS: Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion.

Efficacy of noiiglutide injection on body weight in obese Chinese adults without diabetes: A multicentre, randomized, double-blind, placebo-controlled, phase 2 trial.

AIM: To evaluate the effect of noiiglutide as an adjunct to lifestyle intervention on the reduction in body weight and tolerability in obese Chinese adults without diabetes. MATERIALS AND METHODS: In this 24-week, randomized, double-blind, placebo-controlled phase 2 trial, 254 obese adults with a body mass index of 28.0-40.0 kg/m2 and without diabetes were enrolled. Participants were initially randomized in a 1:1:1 ratio to one of three dose levels: 0.12, 0.24, or 0.36 mg of the study treatment. Within each dose level, participants were further randomized in a 3:1 ratio to receive either subcutaneous injection of noiiglutide or a matching placebo. The primary endpoint was the change in body weight from baseline to week 24. RESULTS: Across all noiiglutide dosage levels, least squares mean reductions in body weight from baseline to week 24 ranged from 8.03 to 8.50 kg, compared with 3.65 kg in the placebo group (all p-values <.0001). In the noiiglutide groups (0.12, 0.24, 0.36 mg/day), a significantly higher proportion of participants achieved a weight loss ≥5% (68.8%, 60.0%, 73.0%) and ≥10% (37.5%, 36.9%, 39.7%), compared with the pooled placebo group (≥5%: 29.0%; ≥10%: 8.1%). Gastrointestinal adverse events, such as nausea, diarrhoea and vomiting, were more common in all noiiglutide groups (15.4%-30.2%, 18.8%-22.2%, 15.6%-18.5%) than in the pooled placebo group (8.1%, 6.5%, 0%). CONCLUSIONS: In obese Chinese adults without diabetes, once-daily subcutaneous noiiglutide significantly reduced body week at week 24 compared with placebo, and had a manageable safety profile, primarily involving gastrointestinal disorders.

Associations between cord blood acetaminophen biomarkers and childhood asthma with and without allergic comorbidities.

BACKGROUND: Previous studies have linked prenatal acetaminophen use to increased asthma risk in children. However, none have explored this association while differentiating between asthma cases with and without other allergic conditions or by employing objective biomarkers to assess acetaminophen exposure. OBJECTIVE: To evaluate whether the detection of acetaminophen biomarkers in cord blood is associated with the subgroups of asthma both with and without allergic comorbidities in children. METHODS: Acetaminophen biomarkers, including unchanged acetaminophen and acetaminophen glucuronide, were measured in neonatal cord blood samples from the Boston Birth Cohort. Asthma subgroups were defined on the basis of physician diagnoses of asthma and other allergic conditions (atopic dermatitis and allergic rhinitis). Multinomial regressions were used to evaluate the associations between acetaminophen biomarkers and asthma subgroups, adjusting for multiple confounders, including potential indications for maternal acetaminophen use such as maternal fever. RESULTS: The study included 142 children with asthma and at least 1 other allergic condition, 55 children with asthma but no other allergic condition, and 613 children free of asthma. Detection of acetaminophen in cord blood, reflecting maternal exposure to acetaminophen shortly before delivery, was associated with 3.73 times the odds of developing asthma without allergic comorbidities (95% CI: 1.79-7.80, P = .0004). In contrast, the detection of acetaminophen in cord blood was not associated with an elevated risk of asthma with allergic comorbidities. Analysis of acetaminophen glucuronide yielded consistent results. CONCLUSION: In a prospective birth cohort, cord blood acetaminophen biomarkers were associated with an increased risk of childhood asthma without allergic comorbidities, but were not associated with childhood asthma with allergic comorbidities.

The evaluation value of atherogenic index of plasma and high-sensitivity C-reactive protein for the degree of coronary artery lesion in premature coronary artery disease.

BACKGROUND: Premature coronary artery disease (PCAD) is prevailing. We aimed to investigate the evaluation value of atherogenic index of plasma (AIP) and high-sensitivity C-reactive protein (hs-CRP) for the occurrence and severity of coronary artery lesion in PCAD patients. METHODS: PCAD (PACD group)/non-PCAD (control group) patients were enrolled. The coronary artery lesion degree was evaluated using Gensini score (GS). PCAD patients were allocated into the low/medium/high GS groups, with general clinical baseline data analyzed. Plasma hs-CRP/AIP levels were compared in PCAD patients with different disease degree. Correlations between plasma hs-CRP/AIP with Gensini score, independent risk factors affecting the occurrence of PCAD, and the predictive value of hs-CRP/AIP/their combination for the occurrence and degree of PCAD were evaluated by Spearman correlation analysis/Logistic multivariate regression/receiver operating characteristic (ROC) curve. The differences in the area under the curve (AUC) were compared using MedCalc-Comparison of ROC curves. RESULTS: Plasma hs-CRP/AIP levels in the PCAD group were increased. Plasma hs-CRP/AIP levels varied significantly among PCAD patients with different disease degree. Plasma hs-CRP/AIP levels were markedly positively correlated with the Gensini score. Smoking history/homocysteine/fasting blood-glucose/hs-CRP/AIP were all independent risk factors affecting PCAD occurrence. The AUC of hs-CRP and AIP combination predicting the occurrence of PCAD was 0.950 (90.80% sensitivity/93.33% specificity). hs-CRP/AIP combination assisted in predicting the disease degree in PCAD patients. CONCLUSIONS: AIP and hs-CRP are independent risk factors for the occurrence of PCAD, and their combination has high predictive value for PCAD occurrence and disease degree, which are both positively correlated with coronary artery lesion degree.

Associations between perceived and actual risk of HIV infection and HIV prevention services uptake among men who have sex with men in Shandong province, China: a cross-sectional study.

BACKGROUND: Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. METHODS: A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. RESULTS: A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P < 0.001). HIV testing uptake had a weak association with perceived high HIV prevalence among social networks (aOR = 1.156, post probability = 0.547). The perceived high HIV prevalence among national MSM was positive related to willingness to use PrEP (aOR = 1.903, post probability = 0.943) and PEP (aOR = 1.737, post probability = 0.829). Perceived personal risk (aOR = 4.486, post probability = 0.994) and perceived HIV prevalence among social networks (aOR = 1.280, post probability = 0.572) were related to history of using PrEP. Perceived personal risk (aOR = 3.144, post probability = 0.952), actual risk (aOR = 1.890, post probability = 0.950), and perceived risk among social networks (aOR = 1.502, post probability = 0.786) were related to history of using PEP. CONCLUSIONS: There is discordance between perceived and actual personal risk of HIV infection among MSM in China. HIV risk assessment and education on HIV prevalence among MSM should be strengthened to assist high-risk populations aware their risk accurately and hence access HIV prevention services proactively.

Mapping the evolving trend of research on Class III malocclusion: a bibliometric analysis.

OBJECTIVES: This study aimed to provide visualized knowledge maps to show the evolving trends and key focal points of Class III malocclusion research through a comprehensive bibliometric analysis. MATERIALS AND METHODS: Class III malocclusion research published between 2000 and 2023 was retrieved from the Web of Science Core Collection. VOSviewer was utilized to count the citation and publication number of authors, institutions, countries and journals. Co-occurrence, co-citation, and cluster analyses and burst detection were conducted using CiteSpace. RESULTS: A total of 3,682 publications on Class III malocclusion were included in the bibliometric analysis. During 2000-2023, both the annual publication count and citation frequency exhibited a gradual upward trajectory, with a noticeable surge in recent years. In terms of production and citation counts of Class III malocclusion research, the core journal is the American Journal of Orthodontics and Dentofacial Orthopedics. Furthermore, apart from the primary keyword 'Class III malocclusion', 'orthognathic surgery' was identified as keyword with the most frequency. The cluster analysis of cited references reveals that the research focal points have shifted to 'skeletal anchorage' and 'surgery-first approach'. Furthermore, the burst detection identified 'quality of life' as a potential research hotspot since it has recently gained increasing scholarly attention. CONCLUSIONS: The current study provides scholars with the knowledge maps of evolving trends and prominent topics of Class III malocclusion research and a summary of research progress on various priorities during different periods. These findings are expected to provide a valuable guidance to facilitate the future research on Class III malocclusion.

Temporomandibular disorder patients with excessive daytime sleepiness present greater pain intensity and reduced jaw function.

BACKGROUND: Sleep disorders are associated with temporomandibular disorders (TMDs). Limited studies have focused on excessive daytime sleepiness (EDS) and its impact on jaw functions in TMD patients. OBJECTIVE: The aim of the present investigation was to identify the impact of EDS on pain and jaw function in TMD patients. METHODS: A total of 338 TMD patients (50 males and 288 females) was included. The Epworth Sleepiness Scale (ESS) was used to classify patients into EDS group (score ≥ 10) and non-EDS group (score < 10). The Jaw Functional Limitation Scale 8-item (JFLS-8) was used to assess the severity of jaw dysfunction. Pain intensity was evaluated using the Visual Analogue Scale (VAS). Anxiety and depression were evaluated using the Generalised Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire 9-item (PHQ-9). All included patients were diagnosed with pain-related TMD (PT), intra-articular TMD (IT) or combined TMD (CT). RESULTS: Compared with non-EDS patients, EDS patients exhibited more severe jaw dysfunction, greater pain intensity and higher PHQ-9 scores (p < .05). Multivariate analyses showed that EDS (B = 3.69), female gender (B = 3.69), and elevated GAD-7 score (B = 0.73) were significantly associated with an increased score on the JFLS-8 (p < .05). Moreover, bivariate logistic regression analysis indicated a significant relationship between EDS and PT (OR = 2.70, p = .007). CONCLUSION: The presence of EDS was more closely related to PT, but the causal relationship between them needs to be further confirmed. More concern and intervention to alleviate poor sleep quality might be highlighted during the treatment of TMD, especially PT subtype.

Virtual Reality Mental Health Interventions in Geriatric Care for Functional or Well-being Enhancement - A Scoping Review.

PURPOSE: It has become common to use Virtual Reality (VR) for mental health interventions; however, its use in care of the elederly is limited, especially regarding mood and well-being. In this review, we summarize the results of current VR-based mental health interventions for this population. METHODS: Peer-reviewed journal articles on immersive VR mental health intervention in seniors, published until 2022, were included. RESULTS: There were 2697 results found in the database search, of which 40 articles met the inclusion criteria and were included in the final analysis. Most studies did not use an experimental design with randomized controlled trials and follow-up sessions. Function-oriented and entertainment-oriented intervention studies were categorized. VR-based geriatric mental interventions have grown rapidly since 2018, especially the number of interventions that promote wellbeing. The function-oriented interventions used active interactions with varied devices. Entertainment-oriented interaction was primarily passive, seldomly using hand controllers for moving activities. Generally, VR interventions improved the mental health of older adults. CONCLUSION: Geriatric rehabilitation can benefit from this innovative technology to maintain cognitive functions and to improve the well-being of seniors. They have potential for use in aging care and in retirement homes. Future VR interventions may also involve promoting social interaction to combat loneliness among seniors.

Knowledge on cause, clinical manifestation and treatment for fibromyalgia among medical doctors: A worldwide survey.

OBJECTIVES: Hench introduced the fibromyalgia syndrome almost 50 years ago. In the meantime, the prevalence has increased, the clinical criteria have changed and the way we explain (chronic) pain has altered. DESIGN: In the current study, we conducted a worldwide survey in which we investigate whether medical doctors are familiar with the American College of Rheumatology (ACR) criteria for fibromyalgia and, if so, whether these medical doctors adhere to the clinical guidelines following evidence-based treatments. RESULTS: In total, 286 medical doctors from 43 countries spread over 6 continents filled out the survey. In most of the countries, the diagnosis fibromyalgia was used. Only 10% adhere to the ACR criteria, widespread pain (44%), unrefreshed sleep (24%), fatigue (20%) and cognitive problems (8%) were most used diagnostic criteria. Of the respondents, 94 (32%) mentioned that the cause is unknown or idiopathic, but also a wide variety of other causes was mentioned. More than 70 different treatment options were provided, of which 24% of the responses were classified as according to the clinical guidelines. From this study, we conclude that many medical doctors do not follow the ACR criteria; the majority has an inappropriate knowledge of causes for fibromyalgia and that a minority of treatment advice adhere to the guidelines.

High-power, sub-100-fs, 1600-1700-nm all-fiber laser for deep multiphoton microscopy.

The 1600-1700-nm ultrafast fiber lasers attract great interests in the deep multiphoton microscopy, due to the reduced levels of the tissue scattering and absorption. Here, we report on the 86.7-MHz, 717-mW, 91.2-fs, all-fiber laser located in the spectral range from 1600 nm to 1700nm. The soliton self-frequency shift (SSFS) was introduced into the Er:Yb co-doped fiber amplifier (EYDFA) to generate the high-power, 1600-1700-nm Raman soliton. Detailed investigations of the nonlinear fiber amplification process were implemented in optimizing the generated Raman soliton pulses. The miniature multiphoton microscopy was further realized with this home-built laser source. The clearly imaging results can be achieved by collecting the generated harmonic signals from the mouse tail skin tissue with a penetration depth of ∼500 µm. The experimental results indicate the great potential in utilizing this 1600-1700-nm fiber laser in the deep multiphoton microscopy.

Efficacy and safety of basal-first titration order in individuals with type 2 diabetes receiving short-term intensive insulin therapy: An exploratory analysis of BEYOND V.

AIMS: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method. MATERIALS AND METHODS: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets. RESULTS: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. CONCLUSIONS: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.

Visualized RNA detection of SARS-CoV-2 in a closed tube by coupling RT-PCR with nested invasive reaction.

A simple, cost-effective and reliable diagnosis of pathogen nucleic acids assay is much required for controlling a pandemic of a virus disease, such as COVID-19. Our previously developed visualized detection of pathogen DNA in a single closed tube is very suitable for POCT. However, virus RNA could not be detected directly and should be reverse-transcribed into cDNA in advance. To enable this visualized assay to detect virus RNA directly, various types of reverse transcriptase were investigated, and finally we found that HiScript II reverse transcriptase could keep active and be well adapted to the one-pot visualized assay in optimized conditions. Reverse transcription, template amplification and amplicon identification by PCR coupled with invasive reaction, as well as visualization by self-assembling of AuNP probes could be automatically and sequentially performed in a closed tube under different temperature conditions, achieving "sample (RNA)-in-result (red color)-out" only by a simple PCR engine plus the naked eye. The visualized RT-PCR is sensitive to unambiguous detection of 5 copies of the N and ORFlab genes of SARS-CoV-2 RNA comparing favourably with qPCR methods (commercialized kit), is specific to genotype 3 variants (Alpha, Beta and Omicron) of SARS-CoV-2, and is very accurate for picking up 0.01% Omicron variant from a large amount of sequence-similar backgrounds. The method is employed in detecting 50 clinical samples, and 10 of them were detected as SARS-CoV-2 positive samples, identical to those by conventional RT-PCR, indicating that the method is cost-effective and labor-saving for pathogen RNA screening in resource-limited regions.

HIV Status Disclosure and Associated Characteristics Among HIV-Positive MSM Receiving Antiretroviral Therapy in Jinan, China.

Disclosure of HIV status offers potential benefits to individuals and is also good for public health. Limited studies have been conducted to gain insight into the current situation and associated factors of HIV disclosure among HIV-positive Chinese men who have sex with men (MSM) in the era of "treat all." We carried out a cross-sectional study among MSM receiving antiretroviral therapy from October 2020 to January 2021 at a hospital in Jinan, China. We used univariate and multivariable logistic regression to examine the factors associated with general disclosure and disclosure to family, friends, and sexual partners. Of the 585 participants recruited, 62.2% reported HIV disclosure, among which 25.3% had disclosed their status to family members, 25.3% had disclosed it to friends, and 28.4% had disclosed it to partners. The findings suggest that HIV disclosure is more likely to occur among individuals who are younger, married/cohabiting, and who self-identify as homosexual/bisexual. Participants with higher education levels or personal monthly incomes are less likely to disclose their HIV status. Furthermore, related factors of disclosure vary across the types of disclosure targets. Given the positive outcomes of disclosure, interventions and implementation research to facilitate it are urgently needed for MSM.

An investigation of the relationships between suicidal ideation, psychache, and meaning in life using network analysis.

BACKGROUND: Previous studies have investigated the relationships between psychache or meaning in life and suicidal ideation based on sum score of corresponding scale. However, this practice has hampered the fine-grained understanding of their relationships. This network analysis study aimed to conduct a dimension-level analysis of these constructs and the relationships among them in a joint framework, and identify potential intervention targets to address suicidal ideation. METHODS: Suicidal ideation, psychache, and meaning in life were measured using self-rating scales among 738 adults. A network of suicidal ideation, psychache, and meaning in life was constructed to investigate the connections between dimensions and calculate the expected influence and bridge expected influence of each node. RESULTS: "Psychache" was positively linked to "sleep" and "despair", while "presence of meaning in life" had negative associations with "psychache", "despair", and "pessimism". The most important central nodes were "sleep" and "despair", and the critical bridge nodes were "presence of meaning in life" and "psychache". CONCLUSION: These preliminary findings uncover the pathological pathways underlying the relationships between psychache, meaning in life, and suicidal ideation. The central nodes and bridge nodes identified may be potential targets for effectively preventing and intervening against the development and maintenance of suicidal ideation.

What Are the Long-term Outcomes of Locking Plates for Nonosteoporotic Three-part and Four-part Proximal Humeral Fractures With a Minimum 10-year Follow-up Period?

BACKGROUND: Proximal humeral fractures (PHFs) often occur in elderly individuals who experience low-energy falls. Open reduction and internal fixation (ORIF) of the proximal humerus is typically performed in young, active patients because of their good bone quality and high functional demands. Although good short-term results have been reported after ORIF in young patients, few studies have specifically evaluated long-term outcomes. QUESTIONS/PURPOSES: (1) What are the long-term clinical outcomes scores and (2) radiologic outcomes of nonosteoporotic three-part and four-part PHFs treated with locking plates? (3) What complications occurred after treatment, and what factors are associated with poor postoperative functional outcomes scores and avascular necrosis (AVN) of the humeral head after ORIF? METHODS: Between June 2005 and December 2012, we surgically treated 774 patients for displaced two-, three-, and four-part PHFs. Approximately 75% (581 of 774) underwent ORIF, 10% (77 of 774) underwent hemiarthroplasty, 7% (54 of 774) underwent intramedullary nailing, 5% (39 of 774) underwent reverse shoulder arthroplasty, and the remaining 3% (23 of 774) underwent other surgical treatments. We considered those who had ORIF as potentially eligible. Based on that criterion, 75% (581) were eligible. However, only patients with nonosteoporotic three- and four-part PHFs (cortical thickness of the proximal humeral diaphysis greater than 6 mm on a preoperative AP radiograph of the affected shoulder) and a minimum of 10 years of follow-up were included. Sixty-four percent (498 of 774) of the patients were excluded because of simple or osteoporotic fractures, 1% (7 of 774) were excluded because of ipsilateral limb multiple fractures, 0.3% (2 of 774) were excluded because of pathologic PHFs, and another 2% (13 of 774) were lost before the minimum study follow-up of 10 years, leaving 8% (61 of 774) for analysis here. The mean age at surgery was 45 ± 12 years, with a mean follow-up of 13 years. Fifty-seven percent (35 of 61) of the patients were men. Patient-reported outcomes were evaluated using the University of California Loas Angeles (UCLA) score (range 0 to 35; higher scores represent better shoulder function) and Constant score (range 0 to 100; higher scores represent better shoulder function) at least 10 years postoperatively. Postoperative radiographs were reviewed to assess the cortical bone thickness of the proximal humerus, neck-shaft angle, head-to-tuberosity distance, and radiologically confirmable complications. Logistic regression analysis was performed to evaluate factors associated with poor postoperative functional scores (UCLA score ≤ 27 or Constant score ≤ 70) and AVN of the humeral head; the association between AVN and postoperative functional outcomes was also assessed. RESULTS: At the most-recent follow-up, these patients had a mean UCLA score of 31 ± 3 and a Constant score of 88 ± 10. The mean neck-shaft angle was 133° ± 10°, and 23% (14 of 61) of patients experienced AVN of the humeral head during follow-up. Twenty-nine complications in 30% (18 of 61) of patients were reported. After controlling for potentially confounding variables such as age and gender, we found that the presence of greater tuberosity malposition (odds ratio 18 [95% confidence interval 2 to 167]; p = 0.01) and immediate postoperative neck-shaft angle less than 130° (OR 19 [95% CI 3 to 127]; p = 0.002) were associated with poor postoperative functional scores. Four-part PHFs (OR 13 [95% CI 2 to 82]; p = 0.008) and metaphyseal extension less than 8 mm (OR 7 [95% CI 1 to 35]; p = 0.03) were associated with AVN of the humeral head. For patients who met the criteria for anatomic reduction (achievement of all of the following three criteria: neck-shaft angle ≥ 130°, head-shaft displacement < 5 mm, and head-to-tuberosity distance greater than or equal to 3 mm and less than or equal to 20 mm), there were no differences in postoperative functional scores between patients with AVN and those without. CONCLUSION: ORIF of nonosteoporotic proximal humeral fractures with locking plates led to favorable functional and radiologic outcomes at a minimum of 10 years of follow-up. When encountering complex PHFs in patients with good bone quality, every effort must be made to achieve an anatomic reduction of the fracture as far as possible, which may not reduce the risk of AVN (this occurred in nearly one-fourth of patients). However, good outcomes can usually be expected, even in patients with AVN. Because this was a retrospective study with a high risk of bias owing to sparse data, the factors associated with poor postoperative functional outcomes must be further investigated in large prospective studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Digital, Crowdsourced, Multilevel Intervention to Promote HIV Testing Among Men Who Have Sex With Men: Cluster Randomized Controlled Trial.

BACKGROUND: Despite great efforts in HIV prevention worldwide, HIV testing uptake among men who have sex with men (MSM) remains suboptimal. The effectiveness of digital, crowdsourced, multilevel interventions in improving HIV testing is still unclear. OBJECTIVE: The aim of this study was to evaluate the effect of a digital, crowdsourced, multilevel intervention in improving HIV testing uptake among MSM in China. METHODS: We conducted a 2-arm cluster randomized controlled trial among MSM in 11 cities in Shandong province, China, from August 2019 to April 2020. Participants were men who were HIV seronegative or had unknown serum status, had anal sex with a man in the past 12 months, and had not been tested for HIV in the past 3 months. Participants were recruited through a gay dating app and community-based organizations from preselected cities; these cities were matched into 5 blocks (2 clusters per block) and further randomly assigned (1:1) to receive a digital, crowdsourced, multilevel intervention (intervention arm) or routine intervention (control arm). The digital multilevel intervention was developed through crowdsourced open calls tailored for MSM, consisting of digital intervention images and videos, the strategy of providing HIV self-testing services through digital tools, and peer-moderated discussion within WeChat groups. The primary outcome was self-reported HIV testing uptake in the previous 3 months. An intention-to-treat approach was used to examine the cluster-level effect of the intervention in the 12-month study period using generalized linear mixed models and the individual-level effect using linear mixed models. RESULTS: A total of 935 MSM were enrolled (404 intervention participants and 531 controls); 751 participants (80.3%) completed at least one follow-up survey. Most participants were younger than 30 years (n=601, 64.3%), single (n=681, 72.8%), had a college degree or higher (n=629, 67.3%), and had an HIV testing history (n=785, 84%). Overall, the proportion of testing for HIV in the past 3 months at the 3-, 6-, 9-, and 12-month follow-ups was higher in the intervention arm (139/279, 49.8%; 148/266, 55.6%; 189/263, 71.9%; and 171/266, 64.3%, respectively) than the control arm (183/418, 43.8%; 178/408, 43.6%; 206/403, 51.1%; and 182/397, 48.4%, respectively), with statistically significant differences at the 6-, 9-, and 12-month follow-ups. At the cluster level, the proportion of participants who had tested for HIV increased 11.62% (95% CI 0.74%-22.5%; P=.04) with the intervention. At the individual level, participants in the intervention arm had 69% higher odds for testing for HIV in the past 3 months compared with control participants, but the result was not statistically significant (risk ratio 1.69, 95% CI 0.87-3.27; P=.11). CONCLUSIONS: The intervention effectively improved HIV testing uptake among Chinese MSM. Our findings highlight that digital, crowdsourced, multilevel interventions should be made more widely available for HIV prevention and other public health issues. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024350; http://www.chictr.org.cn/showproj.aspx?proj=36718. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-020-04860-8.

Gut microbiota may mediate the impact of chronic apical periodontitis on atherosclerosis in apolipoprotein E-deficient mice.

AIM: There are growing evidences linking chronic apical periodontitis (CAP) to atherosclerosis. Gut microbiota is found to be involved in the development of atherosclerosis. Recent studies have shown that CAP could change the diversity and composition of the gut microbiota. It was therefore, we hypothesized that gut microbiota and its metabolites could mediate the impact of CAP on atherosclerosis. METHODOLOGY: Twenty-four 5-week-old lipoprotein E knockout (apoE-/- ) mice were randomly divided into four groups: the CAP group, Con group, Co-CAP (cohoused with CAP) and Co-Con (cohoused with Con) group. In the CAP group, sterile cotton wool containing P. gingivalis was placed into the exposed pulp chamber, followed by coronal resin-based composite restoration of the bilateral maxillary first and second molars. In the Con group, a sham operation was performed. Biweekly, mice in the CAP group were anaesthetised to check the sealing of coronal access. Meanwhile, the animals in the Con group were anaesthetised. The cohousing approach was used to introduce gut microbiota from the CAP and Con groups into the Co-CAP and Co-Con groups, respectively. Alterations in the abundance and diversity of the gut microbiota were detected using 16S rRNA sequencing, Oil-red O staining was used to demonstrate the extent of lesions, and serum levels of trimethylamine N-oxide (TMAO), and immunohistochemistry of flavin-containing monooxygenase 3 (FMO3) in liver were used to assess TMAO-related metabolic alterations. RESULTS: Alterations of alpha and beta diversity were shown both in the CAP and the Co-CAP groups. Moreover, the percentage of atherosclerotic lesion area increased in the CAP and Co-CAP groups (p < .05). Linear discriminant analysis effect size (LEfSe) at the family level found the increases of Lachnospiraceae and Ruminococcaceae (p < .05), which were positively correlated with serum TMAO levels (p < .05). In the redundancy analysis technique (RDA), serum levels of TMAO were positively associated with the atherosclerotic lesions. Co-occurrence analysis revealed that the relative abundances of Lachnospiraceae and Porphyromonadacae were positively correlated with both the percentage of lesion area and TMAO level (p < .05). CONCLUSION: Thus, within the limitations of this study, the data suggest that the gut microbiota can mediate the effects of CAP on atherosclerosis.