Discovery of Dual MER/AXL Kinase Inhibitors as Bifunctional Small Molecules for Inhibiting Tumor Growth and Enhancing Tumor Immune Microenvironment.

A series of bifunctional compounds have been discovered for their dual functionality as MER/AXL inhibitors and immune modulators. The furanopyrimidine scaffold, renowned for its suitability in kinase inhibitor discovery, offers at least three distinct pharmacophore access points. Insights from molecular modeling studies guided hit-to-lead optimization, which revealed that the 1,3-diketone side chain hybridized with furanopyrimidine scaffold that respectively combined amino-type substituent and 1H-pyrazol-4-yl substituent on the top and bottom of the aryl regions to produce 22 and 33, exhibiting potent antitumor activities in various syngeneic and xenograft models. More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8+ T-cells, and helper CD4+ T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 (BPR5K230) with excellent oral bioavailability (F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.

De Garengeot Hernia, an acute appendicitis in the right femoral hernia canal, and successful management with transabdominal closure and appendectomy: a case Report.

Incarceration of the appendix within a femoral hernia is a rare condition of abdominal wall hernia about 0.1 to 0.5% in reported femoral hernia [1]. We report a case of a 56-year-old female whose appendix was trapped in the right femoral canal. There are few reports in the literature on entrapment of the appendix within a femoral hernia. The management of this condition includes antibiotics, drainage appendectomy, hernioplasty and mesh repair.

High-Performance Perovskite Solar Cells and Modules Fabricated by Slot-Die Coating with Nontoxic Solvents.

Energy shortage has become a global issue in the twenty-firt century, as energy consumption grows at an alarming rate as the fossil fuel supply exhausts. Perovskite solar cells (PSCs) are a promising photovoltaic technology that has grown quickly in recent years. Its power conversion efficiency (PCE) is comparable to that of traditional silicon-based solar cells, and scale-up costs can be substantially reduced due to its utilization of solution-processable fabrication. Nevertheless, most PSCs research uses hazardous solvents, such as dimethylformamide (DMF) and chlorobenzene (CB), which are not suitable for large-scale ambient operations and industrial production. In this study, we have successfully deposited all of the layers of PSCs, except the top metal electrode, under ambient conditions using a slot-die coating process and nontoxic solvents. The fully slot-die coated PSCs exhibited PCEs of 13.86% and 13.54% in a single device (0.09 cm2) and mini-module (0.75 cm2), respectively.

The impact of holiday season and weekend effect on traumatic injury mortality: Evidence from a 10-year analysis.

Objectives: Trauma is one of the leading causes of death and its incidence increases annually. The "weekend effect" and "holiday season effect" on traumatic injury mortality remain controversial, whereby traumatic injury patients admitted during weekends and/or holiday season have a higher risk of in-hospital death. The present study is aimed to explore the association between "weekend effect" and "holiday season effect" and mortality in traumatic injury population. Materials and Methods: This retrospective descriptive study included patients from the Taipei Tzu Chi Hospital Trauma Database between January 2009 and June 2019. The exclusion criterion was age of < 20 years. The primary outcome was the in-hospital mortality rate. The secondary outcomes included intensive care unit (ICU) admission, ICU re-admission, length of stay (LOS) in the ICU, ICU admission duration ≥ 14 days, total hospital LOS, total hospital LOS ≥ 14 days, need for surgery, and re-operation rate. Results: In this study, 11,946 patients were included in the analysis, and 8143 (68.2%) patients were admitted on weekdays, 3050 (25.5%) on weekends, and 753 (6.3%) on holidays. Multivariable logistic regression revealed that the admission day was not associated with an increased risk of in-hospital mortality. In other clinical outcome analyses, we found no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups. The subgroup analysis showed that the association between holiday season admission and in-hospital mortality was noted only in the elderly and shock condition populations. The holiday season duration did not differ in terms of in-hospital mortality. Longer holiday season duration was also not associated with an increased risk of in-hospital mortality, ICU LOS ≥14 days, and total LOS ≥14 days. Conclusion: In this study, we did not find any evidence that weekend and holiday season admissions in the traumatic injury population were associated with an increased risk of mortality. In other clinical outcome analyses, there was no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups.

Is N -acetylcysteine effective in treating patients with coronavirus disease 2019? A meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). It has brought tremendous challenges to public health and medical systems around the world. The current strategy for drug repurposing has accumulated some evidence on the use of N -acetylcysteine (NAC) in treating patients with COVID-19. However, the evidence remains debated. METHODS: We performed the systematic review and meta-analysis that complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases and reference lists were searched from inception to May 14, 2022. Studies evaluating the efficacy of NAC in treating patients with COVID-19 were regarded as eligible. The review was registered prospectively on PROSPERO (CRD42022332791). RESULTS: Of 778 records identified from the preliminary search, four studies were enrolled in the final qualitative review and quantitative meta-analysis. A total of 355 patients were allocated into the NAC group and the control group. The evaluated outcomes included intubation rate, improvement, duration of intensive unit stay and hospital stay and mortality. The pooled results showed nonsignificant differences in intubation rate (OR, 0.55; 95% CI, 0.16-1.89; p = 0.34; I2 = 75%), improvement of oxygenation ([MD], 80.84; 95% CI, -38.16 to 199.84; p = 0.18; I2 = 98%), ICU stay (MD, -0.74; 95% CI, -3.19 to 1.71; p = 0.55; I2 = 95%), hospital stay (MD, -1.05; 95% CI, -3.02 to 0.92; p = 0.30; I2 = 90%), and mortality (OR, 0.58; 95% CI, 0.23-1.45; p = 0.24; I2 = 54%). Subsequent trial sequential analysis (TSA) showed conclusive nonsignificant results for mortality, while the TSA for the other outcomes suggested that a larger sample size is essential. CONCLUSIONS: The current evidence reveals NAC is not beneficial for treating patients with COVID- 19 with regard to respiratory outcome, mortality, duration of ICU stay and hospital stay.

Effects of opioids administered via intravenous or epidural patient-controlled analgesia after caesarean section: A network meta-analysis of randomised controlled trials.

Background: Post-caesarean section analgesia is important physiologically and psychologically for both mothers and infants. Patient-controlled analgesia is a well-established method of administering opioids for postoperative pain. However, to date, no study has systematically investigated the effects of opioids administered through intravenous patient-controlled analgesia (IVPCA) or patient-controlled epidural analgesia (PCEA) in parturients who have undergone caesarean section. Methods: This systematic review and network meta-analysis aimed to evaluate the analgesic and adverse effects of opioids administered via IVPCA or PCEA in parturients who have undergone a caesarean section. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception through 02 10, 2022 for relevant records. Randomised controlled trials (RCTs) that compared opioids administered via IVPCA or PCEA and reported outcomes of interest were included. Studies were excluded if the solution for patient-controlled analgesia contained antiemetics and/or other analgesics in addition to opioids. The methodological quality of RCTs was assessed using the revised Cochrane Risk of Bias Tool. Summary data were extracted from each eligible study. The primary outcome was pain intensity, and the secondary outcomes were opioid-related adverse effects. Frequentist network meta-analyses were performed using a contrast-based random-effects model. This study is registered with PROSPERO, CRD42021254040. Findings: Twenty-three studies with 2589 parturients were included. Compared with IVPCA morphine as a reference treatment, PCEA fentanyl had better analgesic effects at 4 h (mean difference [MD] in the visual analogue scale score, -0.75; 95% confidence interval [CI] [-1.16, -0.34]) and 8 h (MD, -0.93; 95% CI [-1.57, -0.28]) and yielded lower odds of developing nausea/vomiting (odds ratio [OR], 0.27; 95% CI [0.09, 0.80]) and sedation/drowsiness (OR, 0.22; 95% CI [0.11, 0.45]). However, PCEA fentanyl may be more likely to cause pruritus than IVPCA treatments. Interpretation: Considering the analgesic efficacy; opioid-induced nausea, vomiting, and sedation; and the well-being of breastfed infants, PCEA fentanyl may be the treatment of choice for post-caesarean section analgesia. Funding: The Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-111-27).

Validation of cardiac output estimation using the fourth-generation FloTrac/EV1000™ system in patients undergoing robotic-assisted off-pump coronary artery bypass surgery.

The pulmonary artery catheter (PAC)-despite its invasiveness-remains the gold standard for cardiac output (CO) monitoring. The FloTrac system, a less invasive hemodynamic monitor has been developed, which estimates CO using arterial pressure waveform analysis without external calibration. Recently, an upgraded version of FloTrac system with improved algorithm to follow changes in vascular resistance was introduced into the market. The aim of this study was to assess the reliability of the CO estimated from the fourth-generation FloTrac/EV1000 system (COFT) compared to that measured with PAC using the thermodilution method (COPAC) during robotic-assisted off-pump coronary artery bypass (OPCAB) surgery. COFT and COPAC were obtained simultaneously at 4 predefined time points during robotic-assisted OPCAB: 5 min after the induction of general anesthesia (T1), after starting one-lung ventilation (T2), after capnothorax (T3), and after mini-thoracotomy was performed (T4). The agreement of data was investigated by Bland-Altman analysis. Thirty-four patients were initially enrolled. After exclusion, 32 patients and a total of 128 paired CO measurements were obtained. The overall bias was 1.46 L/min, the 95% limits of agreements were - 3.40 to 6.33 L/min, and the percentage error was 72.98%. Regression analysis of the systemic vascular resistance index (SVRI) and the bias between COPAC and COFT showed that the bias was moderately correlated with the SVRI (r2 = 0.43; p < 0.0001). Despite a software upgrade, the reliability of the fourth-generation FloTrac/EV1000™ system during robotic-assisted OPCAB to estimate CO was not acceptable, especially in patients with low SVRI.

Shock index, modified shock index, age shock index score, and reverse shock index multiplied by Glasgow Coma Scale predicting clinical outcomes in traumatic brain injury: Evidence from a 10-year analysis in a single center.

Objectives: Early identification of traumatic brain injury (TBI) patients at a high risk of mortality is very important. This study aimed to compare the predictive accuracy of four scoring systems in TBI, including shock index (SI), modified shock index (MSI), age-adjusted shock index (ASI), and reverse shock index multiplied by the Glasgow Coma Scale (rSIG). Patients and methods: This is a retrospective analysis of a registry from the Taipei Tzu Chi trauma database. Totally, 1,791 patients with TBI were included. We investigated the accuracy of four major shock indices for TBI mortality. In the subgroup analysis, we also analyzed the effects of age, injury mechanism, underlying diseases, TBI severity, and injury severity. Results: The predictive accuracy of rSIG was significantly higher than those of SI, MSI, and ASI in all the patients [area under the receiver operating characteristic curve (AUROC), 0.710 vs. 0.495 vs. 0.527 vs. 0.598], especially in the moderate/severe TBI (AUROC, 0.625 vs. 0.450 vs. 0.476 vs. 0.529) and isolated head injury populations (AUROC 0.689 vs. 0.472 vs. 0.504 vs. 0.587). In the subgroup analysis, the prediction accuracy of mortality of rSIG was better in TBI with major trauma [Injury Severity Score (ISS) ≥ 16], motor vehicle collisions, fall injury, and healthy and cardiovascular disease population. rSIG also had a better prediction effect, as compared to SI, MSI, and ASI, both in the non-geriatric (age < 65 years) and geriatric (age ≥ 65 years). Conclusion: rSIG had a better prediction accuracy for mortality in the overall TBI population than SI, MSI, and ASI. Although rSIG have better accuracy than other indices (ROC values indicate poor to moderate accuracy), the further clinical studies are necessary to validate our results.

Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis.

Purpose: Metformin is a biguanide derivative that is commonly used for the treatment of diabetes mellitus (DM). It demonstrates antioxidative, anti-inflammatory, and antiangiogenic activity within the ocular tissue and thus may be implicated in the treatment of age-related macular degeneration (AMD). However, epidemiological studies have shown conflicting results. Methods: The Ovid MEDLINE/Embase, Cochrane Library, and Web of Science databases were systematically searched from inception through August 3, 2022. Studies reporting the association between metformin use and odds of AMD were enrolled. Adjusted odds ratios (ORs) of AMD were extracted and pooled with random-effects model meta-analysis. Subgroup analyses based on AMD subtypes, ethnicity, study design, sex, and confirmation of AMD diagnosis were conducted. Results: A total of 9 observational studies with 1,446,284 participants were included in the analysis. The meta-analysis showed that metformin use was associated with a significant reduction in the odds of AMD (pooled ORs = 0.81, 95% confidence interval [CI] = 0.70-0.93). Subgroup analyses revealed that metformin use was not significantly associated with dry or wet AMD. Black (pooled ORs = 0.61, 95% CI = 0.58-0.64) and Hispanic populations (pooled ORs = 0.85, 95% CI = 0.81-0.89) demonstrated significantly lower odds of AMD. Conclusions: This systematic review and meta-analysis found that patients with DM with metformin usage were at lower odds of developing AMD. Future prospective clinical trials are needed to confirm this association.

Association of In-Hospital Mortality and Trauma Team Activation: A 10-Year Study.

Background: Early trauma team activation (TTA) may improve clinical outcomes through early diagnosis and timely intervention by a dedicated multidisciplinary team. Controversy seems to exist about the effect of establishing trauma team systems in traumatic injury populations. Our aim was to identify factors that may be associated with clinical outcomes in trauma injury and to investigate the effect of trauma team activation. Method: This retrospective descriptive study included all traumatic patients from the Taipei Tzu Chi Hospital Trauma Database. All prehospital vital signs, management, injury type, injury mechanisms, hospitalization history, and clinical outcomes were analyzed, and multivariable logistic regression was used to investigate the association between trauma team activation and clinical outcomes. Subgroups of TTA in minor injury and non-TTA in major injury were also analyzed. Result: In this study, a total of 11,946 patients were included, of which 10,831 (90.7%) patients were minor injury (ISS < 16), and 1115 (9.3%) patients were major injury (ISS ≥ 16). In the minor injury population, TTA had a higher intensive care unit (ICU) admission rate, operation rate, re-operation rate, and prolonged total length of stay (LOS). In the major injury population, TTA had a higher mortality rate, prolonged total LOS, and prolonged ICU LOS. After adjusting for mechanism of injury and injury severity, there was no association between in-hospital mortality and TTA, compared with the non-TTA group. However, the TTA group had a higher risk of ICU admission, prolonged ICU LOS, and prolonged total LOS. The subgroup analysis showed trauma team activation had a higher risk of mortality in the 60- to 80-year-old population, major injury (ISS ≥ 16), consciousness clear population, and non-head injury group. Conclusions: We found there was no significant association between in-hospital mortality and TTA. However, in the TTA group, there was a higher risk of ICU admission, prolonged total, LOS, and prolonged ICU LOS. In the subgroup analysis, TTA had a higher risk of mortality in the 60- to 80-year-old population, major injury (ISS ≥ 16), consciousness clear population, and non-head injury group. Our results reflect TTA-criteria-selected patients with greater ISS and a high risk of mortality.

Effects of Short-Acting Opioids on Intraocular Pressure during General Anesthesia: Systematic Review and Network Meta-Analysis.

Intraocular pressure (IOP) is crucial to the well-being of eyes. During anesthesia, the administration of succinylcholine and endotracheal intubation are associated with an increase in IOP, which may be attenuated by short-acting opioids. However, the drug of choice among the commonly used short-acting opioids is unclear. This study aimed to evaluate the effects of fentanyl, sufentanil, alfentanil, and remifentanil on IOP measured after the administration of succinylcholine and after endotracheal intubation in patients undergoing general anesthesia. Five databases were searched. Randomized controlled trials (RCTs) that compared short-acting opioids and reported at least one of the clinical outcomes of interest were included. Nine RCTs with 357 patients were included. Remifentanil (1 µg kg-1) more effectively alleviated the increase in IOP than the placebo after the administration of succinylcholine [mean difference (MD) of IOP, -3.64; confidence interval (CI), -5.47 to -1.81 and after endotracheal intubation (MD, -9.71; CI, -11.91 to -7.51). Remifentanil (1 µg kg-1) ranked the best in terms of both attenuating the increase in IOP after the administration of succinylcholine [surface under the cumulative ranking curve (SUCRA), 0.91; normalized entropy (NE), 0.47; and after endotracheal intubation (SUCRA, 0.89; NE, 0.54) among all of the treatments. Remifentanil (1 µg kg-1) should be considered the drug of choice in the circumstances where increased IOP is a great concern.

Combination Therapy and Single-Modality Treatment for Acute Low-Tone Hearing Loss: A Meta-Analysis with Trial Sequential Analysis.

Acute low-tone hearing loss (ALHL) is a common clinical disease and was first proposed by Abe in 1981 as sensorineural hearing loss confined to low frequencies. The best strategy for initiating medication is still unclear, as the superiority of steroids and diuretics is still debated, and combination therapy might yield additional benefits. However, no study regarding combination therapy has been published. The objective of this study was to evaluate the efficacy of steroid therapy versus combination therapy of diuretics with steroids by conducting a systematic review with a meta-analysis and trial sequential analysis (TSA). Studies enrolling patients with a diagnosis of acute low-tone hearing loss were considered eligible. After searching the PubMed, Cochrane Library, Embase, Scopus and Web of Science databases from inception to 31 December 2021, five studies including 433 patients were enrolled. Overall, the comparison between combination therapy with steroids and diuretics and single-modality treatment with steroids (OR, 1.15; 95% CI, 0.51 to 2.59; p = 0.74; I2 = 34%) and the comparison between combination therapy and treatment with diuretics alone (OR, 1.73; 95% CI, 0.93 to 3.23; p = 0.09; I2 = 5%) showed that combination therapy did not confer significant benefits when compared to single-modality treatments. A trial sequential analysis (TSA) showed conclusive nonsignificant results of the comparison between the combination of steroids and diuretics and a single-modality treatment. In conclusion, we reported that the combination of steroids and diuretics did not yield significant benefits when compared to single-modality treatment with steroids or diuretics. We suggest that treatment should be initiated with steroids or diuretics alone to avoid potential adverse effects.

The association between blood pressure and in-hospital mortality in traumatic brain injury: Evidence from a 10-year analysis in a single-center.

OBJECTIVE: Blood pressure in patients with traumatic brain injury (TBI) is associated with clinical outcome. However, evidence of blood pressure (BP) range is scarce and the association between BP and clinical outcome is mostly controversial. We aimed to investigate the association between blood pressure and clinical outcome in TBI. METHODS: This is a retrospective cohort study using the Taipei Tzu Chi Hospital trauma database from January 2009 to June 2019; totally, 13,114 patients were examined. The primary outcome of this investigation was in-hospital mortality and the secondary outcomes were intensive care unit (ICU) admission rate and prolong ICU stay (defined as stay in ICU ≥ 14 days). Subgroups analysis of Glasgow Coma Scale (GCS) and Triage SBP was also conducted. RESULTS: A total of 1782 traumatic adult patients with TBI (AIS score < 3) were finally included. The cut-off points are 130 mmHg to 149 mmHg in all TBI patients with lower odds ratio of mortality. In different TBI severity, U-shape relationship also presented and we also found that cut-off points of 130 to 149 mmHg in mild TBI and 110 to 129 mmHg in moderate TBI have lower odds ratio of mortality. The mortality is significantly increased in BP below 90 mmHg and above 190 mmHg in TBI patients. CONCLUSIONS: Traumatic brain injury population presented a U-shape relationship between triage SBP and in-hospital mortality. Early resuscitation and correct hypotension/hypertension in TBI population with BP below 90 mmHg and above 190 mmHg may prevent from increased mortality.

Comparison of personal sound amplification products and conventional hearing aids for patients with hearing loss: A systematic review with meta-analysis.

Background: Hearing loss is a common morbidity that requires a hearing device to improve quality of life and prevent sequelae, such as dementia, depression falls, and cardiovascular disease. However, conventional hearing aids have some limitations, including poor accessibility and unaffordability. Consequently, personal sound amplification products (PSAPs) are considered a potential first-line alternative remedy for patients with hearing loss. The main objective of this study was to compare the efficacy of PSAPs and conventional hearing aids regarding hearing benefits in patients with hearing loss. Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases and reference lists were searched from inception to January 12, 2022. Studies including randomised, controlled trials; nonrandomised, controlled trials; or observational studies comparing PSAPs and hearing aids with regard to hearing gain performance (e.g., speech intelligence) were considered eligible. The review was registered prospectively on PROSPERO (CRD42021267187). Findings: Of 599 records identified in the preliminary search, five studies were included in the review and meta-analysis. A total of 124 patients were divided into the PSAP group and the conventional hearing aid group. Five studies including seven groups compared differences for speech intelligence in the signal-noise ratio (SNR) on the hearing in noise test (HINT) between PSAPs and conventional hearing aids. The pooled results showed nonsignificant differences in speech intelligence (SMD, 0.14; 95% CI, -0.19 to 0.47; P = .41; I 2=65%), sound quality (SMD, -0.37; 95% CI, -0.87 to 0.13; P = .15; I 2=77%) and listening effort (SMD 0.02; 95% CI, -0.24 to 0.29; P = .86; I 2=32%). Nonsignificant results were also observed in subsequent analyses after excluding patients with moderately severe hearing loss. Complete sensitivity analyses with all of the possible combinations suggested nonsignificant results in most of the comparisons between PSAPs and conventional hearing aids. Interpretation: PSAPs are potentially beneficial as conventional hearing aids are in patients with hearing loss. The different features among PSAPs should be considered for patients indicated for hearing devices. Funding: This work was supported by grants from Ministry of Science and Technology (MOST-10-2622-8-075-001) and Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST111-G6-11-2 and VGHUST111c-140).

Smartphone-Enabled versus Conventional Otoscopy in Detecting Middle Ear Disease: A Meta-Analysis.

Traditional otoscopy has some limitations, including poor visualization and inadequate time for evaluation in suboptimal environments. Smartphone-enabled otoscopy may improve examination quality and serve as a potential diagnostic tool for middle ear diseases using a telemedicine approach. The main objectives are to compare the correctness of smartphone-enabled otoscopy and traditional otoscopy and to evaluate the diagnostic confidence of the examiner via meta-analysis. From inception through 20 January 2022, the Cochrane Library, PubMed, EMBASE, Web of Science, and Scopus databases were searched. Studies comparing smartphone-enabled otoscopy with traditional otoscopy regarding the outcome of interest were eligible. The relative risk (RR) for the rate of correctness in diagnosing ear conditions and the standardized mean difference (SMD) in diagnostic confidence were extracted. Sensitivity analysis and trial sequential analyses (TSAs) were conducted to further examine the pooled results. Study quality was evaluated by using the revised Cochrane risk of bias tool 2. Consequently, a total of 1840 examinees were divided into the smartphone-enabled otoscopy group and the traditional otoscopy group. Overall, the pooled result showed that smartphone-enabled otoscopy was associated with higher correctness than traditional otoscopy (RR, 1.26; 95% CI, 1.06 to 1.51; p = 0.01; I2 = 70.0%). Consistently significant associations were also observed in the analysis after excluding the simulation study (RR, 1.10; 95% CI, 1.00 to 1.21; p = 0.04; I2 = 0%) and normal ear conditions (RR, 1.18; 95% CI, 1.01 to 1.40; p = 0.04; I2 = 65.0%). For the confidence of examiners using both otoscopy methods, the pooled result was nonsignificant between the smartphone-enabled otoscopy and traditional otoscopy groups (SMD, 0.08; 95% CI, -0.24 to 0.40; p = 0.61; I2 = 16.3%). In conclusion, smartphone-enabled otoscopy was associated with a higher rate of correctness in the detection of middle ear diseases, and in patients with otologic complaints, the use of smartphone-enabled otoscopy may be considered. More large-scale studies should be performed to consolidate the results.

Efficacy of Ventilation Tube Insertion with Palatal Repair for Otitis Media in Cleft Palate: Meta-Analysis and Trial Sequential Analysis.

Cleft palate is the most common congenital facial deformity and may result in multiple sequelae and disabilities. One common comorbidity is refractory otitis media with effusion (OME), as patients with cleft palate have impaired eustachian tube function with alteration of the nearby muscular structures. Ventilation tube insertion (VTI) is regarded as an effective mean to address OME in addition to palatal repair surgery. However, controversy regarding the efficacy of VTI and the timing of VTI remains. We aimed to assess the efficacy of VTI with palatal repair for cleft palate on OME development via a meta-analysis with systematic review and trial sequential analysis (TSA). Studies including patients with cleft palate who underwent palatal repair with or without VTI were considered eligible. After searching the Cochrane Library, PubMed, EMBASE, Web of Science, Scopus and China National Knowledge Infrastructure (CNKI) from inception through 5 September 2021, 9 studies involving 929 patients were included. Overall, a significantly higher OME-free rate was noted in those who underwent VTI and palatal repair than in those who underwent palatal repair alone (OR, 2.73; 95% CI, 1.37 to 5.42; p = 0.004; I2 = 84%). Subgroup analysis revealed that the OME-free rate remained higher in the concurrent VTI group (OR, 3.29; 95% CI, 1.64 to 6.59; p < 0.001; I2 = 81%). TSA indicated that all the analyses provided conclusive results by meeting the required information size and Z-value. The meta-analysis indicated that VTI is an effective procedure to prevent OME in patients with cleft palate and that VTI is beneficial when performed concurrently with palatal repair surgery.

Face-Down Posture versus Non-Face-Down Posture following Large Idiopathic Macular Hole Surgery: A Systemic Review and Meta-Analysis.

Evidence regarding the effect of a face-down posture (FDP) for large idiopathic macular hole (IMH) is inconsistent. We conducted a systematic review and meta-analysis to determine whether a postoperative FDP is required for the treatment of large IMH. Eligible randomized controlled trials published before September 2021 were retrieved from the Medline, Embase, and Cochrane Library databases. The efficacy outcome was the IMH closure rate and the visual acuity improvement rate. A meta-analysis was performed using a random effects model. The "Grading of Recommendations Assessment, Development, and Evaluation" approach was implemented, and the numbers needed-to-treat (NNTs) were calculated. Seven studies comprising 640 patients were included. We performed a predefined subgroup analysis of IMH size using a cut-off point of 400 µm. Compared with non-FDP, a significant effect of FDP was found in the IMH > 400 µm group (OR = 3.34; 95% CI = 1.57-7.14; trial sequential analysis-adjusted CI = 1.20-11.58; NNTs = 7.9). After stratifying by the posturing periods, the beneficial effect of FDP lasting at least five days, but not three days was observed for large IMH. Maintaining a FDP for at least five days postoperatively is an effective strategy (certainty of evidence: "moderate") for treating large IMH.

Annealing Effect on the Characteristics of Co40Fe40W10B10 Thin Films on Si(100) Substrate.

This research explores the behavior of Co40Fe40W10B10 when it is sputtered onto Si(100) substrates with a thickness (tf) ranging from 10 nm to 100 nm, and then altered by an annealing process at temperatures of 200 °C, 250 °C, 300 °C, and 350 °C, respectively. The crystal structure and grain size of Co40Fe40W10B10 films with different thicknesses and annealing temperatures are observed and estimated by an X-ray diffractometer pattern (XRD) and full-width at half maximum (FWHM). The XRD of annealing Co40Fe40W10B10 films at 200 °C exhibited an amorphous status due to insufficient heating drive force. Moreover, the thicknesses and annealing temperatures of body-centered cubic (BCC) CoFe (110) peaks were detected when annealing at 250 °C with thicknesses ranging from 80 nm to 100 nm, annealing at 300 °C with thicknesses ranging from 50 nm to 100 nm, and annealing at 350 °C with thicknesses ranging from 10 nm to 100 nm. The FWHM of CoFe (110) decreased and the grain size increased when the thickness and annealing temperature increased. The CoFe (110) peak revealed magnetocrystalline anisotropy, which was related to strong low-frequency alternative-current magnetic susceptibility (χac) and induced an increasing trend in saturation magnetization (Ms) as the thickness and annealing temperature increased. The contact angles of all Co40Fe40W10B10 films were less than 90°, indicating the hydrophilic nature of Co40Fe40W10B10 films. Furthermore, the surface energy of Co40Fe40W10B10 presented an increased trend as the thickness and annealing temperature increased. According to the results, the optimal conditions are a thickness of 100 nm and an annealing temperature of 350 °C, owing to high χac, large Ms, and strong adhesion; this indicates that annealing Co40Fe40W10B10 at 350 °C and with a thickness of 100 nm exhibits good thermal stability and can become a free or pinned layer in a magnetic tunneling junction (MTJ) application.

Discovery of BPR1R024, an Orally Active and Selective CSF1R Inhibitor that Exhibits Antitumor and Immunomodulatory Activity in a Murine Colon Tumor Model.

Colony-stimulating factor-1 receptor (CSF1R) is implicated in tumor-associated macrophage (TAM) repolarization and has emerged as a promising target for cancer immunotherapy. Herein, we describe the discovery of orally active and selective CSF1R inhibitors by property-driven optimization of BPR1K871 (9), our clinical multitargeting kinase inhibitor. Molecular docking revealed an additional nonclassical hydrogen-bonding (NCHB) interaction between the unique 7-aminoquinazoline scaffold and the CSF1R hinge region, contributing to CSF1R potency enhancement. Structural studies of CSF1R and Aurora kinase B (AURB) demonstrated the differences in their back pockets, which inspired the use of a chain extension strategy to diminish the AURA/B activities. A lead compound BPR1R024 (12) exhibited potent CSF1R activity (IC50 = 0.53 nM) and specifically inhibited protumor M2-like macrophage survival with a minimal effect on antitumor M1-like macrophage growth. In vivo, oral administration of 12 mesylate delayed the MC38 murine colon tumor growth and reversed the immunosuppressive tumor microenvironment with the increased M1/M2 ratio.