INTRODUCTION: Cancer causes significant morbidity and mortality in the United States. It is the second most common cause of death in the United States, after heart disease. African Americans are disproportionately affected by malignancy, with overall higher death rates compared to other racial and ethnic groups. Screening tests can identify early stage malignancy allowing for timely intervention. However, African Americans less frequently undergo cancer screening. Advancement in genomic technology has led to the identification of signals for cancer in the blood. This has resulted in the development of multi-cancer early detection (MCED) tests which evaluate for circulating cell-free DNA (cfDNA). This study evaluated physicians\' perception of the use of a multi-cancer early detection test (MCED).
METHODS: An anonymous, 29 question survey was administered to African American / Black physicians and medical students. Survey participants were identified through the National Medical Association and other professional organizations that included primarily African American physicians. Surveys were excluded from analysis if respondent was non-African American / Black or was not a physician or medical student. The survey collected physician demographics, percentage of African American / Black patients in their practice, patient barriers to screening, potential use of MCED tests and factors influencing decision to recommend testing. Descriptive statistics were generated. Additional analysis was performed using Chi-Square with statistical significance set at p-value <0.05. The survey was pilot tested for reliability and validity.
RESULTS: 1196 (681 female, 515 male) physicians and medical students completed the survey. 95.8 % were physicians who were or had been in clinical practice. Fifty-three percent of physicians reported that >40 % of their patients were African American / Black. Barriers to cancer screening included lack of understanding of the importance (33.8 %), lack of or limited insurance coverage (23.5 %), socioeconomic factors unrelated to insurance coverage (16.2 %), fear of cancer (8.8 %), history of racism and bias in the health care system (7.4 %) with 8.8 % reporting \'other\' and 1.5 % reporting no perceived barriers. There was a significant difference (p<0.03) in the rate that physicians\' perceived racism and bias in the health care system as barrier for cancer screening in African American / Black patients when compared to other patients. Most physicians and medical students indicated that a MCED test would benefit all patients (86.8 %), would encourage further cancer screening tests (83.8 %), and would be beneficial for minority and under-represented patients regardless of socioeconomics or health care access (83.8 %). Seventy-five percent of survey respondents indicated that a MCED test would be beneficial in promoting further cancer screening and early detection in African American / Black patients. Factors that would impact the ordering of an MCED test included scientific evidence and test validity (63.2 %), efficiency, accessibility, ease of ordering and ease of receiving results (11.8 %), insurance coverage (13.2 %) and \'other factors\' (11.8 %).
CONCLUSIONS: This is one of the largest surveys to assess physicians\' perceptions about MCED testing and is the first study to evaluate the perspectives of African American physicians. It offers insight about physician acceptance and potential incorporation of MCED into clinical practice. It is important that a multifaceted approach is employed to improve cancer outcomes and reduce disparities in survival. MCED tests, a relatively new advancement in genomic technology, have the potential to be an important component in cancer screening strategies.

The aim of this network meta-analysis was to compare the efficacy of various commonly used drugs in treating patients with hypertrophic cardiomyopathy (HCM). Randomized controlled trials on drugs for HCM treatment were retrieved from PubMed, Embase, Cochrane Library, and Web of Science (search cutoff: January 10, 2024). Quality assessment was performed using the risk of bias tool, and data analysis used R software. Seventeen studies (1,133 patients with HCM) were included. The network meta-analysis indicated that mavacamten and perhexiline improved peak oxygen consumption compared with placebo. Mavacamten reduced N-terminal pro-B-type natriuretic peptide, left ventricular mass index, left atrial volume index, and septal E/e\' ratio. Losartan decreased systolic blood pressure, whereas candesartan, mavacamten, and valsartan reduced maximum wall thickness. Perhexiline had better efficacy in increasing peak oxygen consumption, and candesartan in reducing maximum wall thickness. No drug significantly improved left ventricular ejection fraction compared with placebo. In conclusion, on the basis of current studies, commonly used drugs may effectively improve some of the outcome measures in patients with HCM, whereas the novel drug mavacamten showed significant therapeutic effects in most of the remaining outcome measures except for left ventricular ejection fraction.

UNASSIGNED: Sodium glucose cotransporter-2 inhibitors (SGLT2is) have gained immense attention for a variety of indications. Limb amputations (LA) and fractures were reported in clinical trials. This network meta-analysis and meta-regression were carried out to quantify the risks of these events.
UNASSIGNED: Randomized clinical trials evaluating SGLT2is and reporting patients developing LA/fracture were included. Odds ratios (OR) with 95% confidence intervals (95% CI) were the effect estimates. Sub-group analyses and meta-regression analysis were carried out.
UNASSIGNED: Ninety articles were included (LA: 36 studies; 96522 participants and fracture: 66 studies; 102,862 participants). An increased risk of LA (OR: 1.2; 95% CI: 1.1, 1.3) was observed. Amongst SGLT2is, canagliflozin was associated with increased risk of LA (OR: 1.6, 95% CI: 1.1, 2.4) while dapagliflozin with fracture (OR: 1.1, 95% CI: 1, 1.2). Sub-group analysis revealed increased risk of LA with an OR of 1.3 among those in the age group of > 40 to < 65, body-mass index of > 30 kg/m2, HbA1c category of > 7%, duration of diabetes of > 10 years, type 2 diabetes, and an OR of 1.2 for SGLT2is administration of > 6 months.
UNASSIGNED: SGLT2is were observed with an increased risk of LA. High- risk categories were identified for which precautions should be recommended in the standard treatment guidelines.
UNASSIGNED: Open Science Framework (https://osf.io/5fwyk).

UNASSIGNED: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, often diagnosed at an advanced stage. Systemic chemotherapy is the primary treatment, but direct comparisons of different regimens are limited. This study conducted a systematic review and network meta-analysis (NMA) to compare the efficacy and safety of various chemotherapy regimens, with the unique advantage of only including Phase III randomized controlled trials (RCTs).
UNASSIGNED: NMA was conducted regarding the searched phase III RCTs by comparing overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of different chemotherapy protocols.
UNASSIGNED: The analysis included 24 studies with 11470 patients across 25 treatment modalities. Among the chemotherapy regimens evaluated, FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) demonstrated the highest OS and PFS, with a risk ratio (logHR) of 4.5 (95 % confidence interval 4.32-4.68) compared to gemcitabine monotherapy. The PEFG regimen (cisplatin, epirubicin, 5-fluorouracil, and gemcitabine) exhibited the highest ORR, with an odds ratio (OR) of 6.67 (2.08-20) compared to gemcitabine monotherapy. Notably, gemcitabine plus sorafenib was associated with the lowest hematological toxicity, with an odds ratio (OR) of 0.1 (0.02-0.48).
UNASSIGNED: Combination therapies may offer greater benefits but also cause more toxic effects. However, combinations with targeted agents seem to have fewer adverse reactions.

UNASSIGNED: Fibromyalgia (FM) is a prevalent chronic disorder characterized by widespread skeletal muscle pain. In recent years, complementary and alternative medicine (CAM) has increasingly been recognized for its potential in treating FM symptoms. This study aims to assess the efficacy of CAM therapies in mitigating the symptoms of FM.
UNASSIGNED: This systematic review was registered with INPLASY. A thorough search of both English and Chinese databases was undertaken from their inception until April 15, 2023. The search criteria focused on prospective controlled trials examining CAM therapies in FM patients. The statistical analysis employed mean values and standard deviations. Additionally, an evaluation of the literature\'s quality and potential biases was conducted.
UNASSIGNED: The search yielded 41 articles, encompassing 2877 FM patients and involving 20 different interventions. All studies were randomized controlled trials (RCTs). The results of the network meta-analysis (NMA) indicated that a combination of Acupuncture and Massage therapy, as well as Navel Needling therapy, effectively alleviated pain symptoms in FM patients. Furthermore, Abdominal Acupuncture and Electroacupuncture were found to be beneficial in improving patients\' mood and sleep quality.
UNASSIGNED: Acupuncture + Massage and Umbilical Acupuncture emerged as the most efficacious therapies in relieving pain symptoms in FM patients. Abdominal Acupuncture and Electroacupuncture demonstrated their effectiveness in enhancing mood and sleep quality. Overall, CAM therapies exhibited a high safety profile for patients with fibromyalgia.

Oral cancer became a very common condition. WHO estimates that there are 4 cases of lip and oral cavity cancer for every 100,000 people worldwide. The early diagnosis of cancers is currently a top focus in the health sector. Recent systematic reviews and meta-analyses have identified promising biomarkers for early detection in several original research investigations. However, it is still unclear the quality of these evidence and which biomarker performs the best in terms of early detection. Therefore, the objective was, to map the methodological and reporting quality of available oral squamous cell carcinoma (OSCC) or head/neck squamous cell carcinoma (HNSCC) systematic reviews and meta-analysis. Secondly, to evaluate diagnostic accuracy of salivary biomarkers for common craniofacial cancers and to compare the diagnostic value of different salivary biomarkers. PubMed, Scopus, Web of Science, Embase and Cochrane Library electronic databases were used to map the methodological and reporting quality of the systematic reviews and meta-analysis conducted on the HNSCC, OSCC using the AMSTAR-2 checklist. The inclusion criteria were systematic reviews and meta-analysis published in the topic of HNSCC and OSCC biomarkers. Exclusion criteria were no animal studies; original primary studies, due to limitation of competency in other languages articles with language other than English were excluded. The sensitivity and specificity were calculated for salivary biomarkers and ranked according to network meta-analysis principles. A total of N = 5893 patients were included from four meta-analysis studies. All together, these included n = 37 primary studies. n = 94 biomarkers were pooled from these four meta-analyses and categorised into the stages at which they were detected (I-IV). In OSCC, Chemerin and MMP-9 displayed the highest sensitivity, registering 0.94 (95% CI 0.78, 1.00) and a balanced accuracy of 0.93. Phytosphingosine closely followed, with a sensitivity of 0.91 (95% CI 0.68, 0.99) and a balanced accuracy of 0.87. For HNSCC, the top three biomarkers are Actin, IL-1β Singleplex, and IL-8 ELISA. Actin leads with a sensitivity of 0.91 (95% CI 0.68-0.99), a specificity of 0.67, and an overall accuracy of 0.79. Subsequently, IL-1β Singleplex exhibits a sensitivity of 0.62 (95% CI 0.30-0.88), a specificity of 0.89, and an accuracy of 0.75, followed by IL-8 ELISA with a sensitivity of 0.81 (95% CI 0.54-0.97), a specificity of 0.59, and an accuracy of 0.70. In conclusion, there was highest sensitivity for MMP-9 and chemerin salivary biomarkers. There is need of further more studies to identify biomarkers for HNSCC and OSCC.

The reliability of the results of network meta-analysis (NMA) lies in the plausibility of the key assumption of transitivity. This assumption implies that the effect modifiers\' distribution is similar across treatment comparisons. Transitivity is statistically manifested through the consistency assumption which suggests that direct and indirect evidence are in agreement. Several methods have been suggested to evaluate consistency. A popular approach suggests adding inconsistency factors to the NMA model. We follow a different direction by describing each inconsistency factor with a candidate covariate whose choice relies on variable selection techniques. Our proposed method, stochastic search inconsistency factor selection (SSIFS), evaluates the consistency assumption both locally and globally, by applying the stochastic search variable selection method to determine whether the inconsistency factors should be included in the model. The posterior inclusion probability of each inconsistency factor quantifies how likely is a specific comparison to be inconsistent. We use posterior model odds or the median probability model to decide on the importance of inconsistency factors. Differences between direct and indirect evidence can be incorporated into the inconsistency detection process. A key point of our proposed approach is the construction of a reasonable \"informative\" prior concerning network consistency. The prior is based on the elicitation of information derived historical data from 201 published network meta-analyses. The performance of our proposed method is evaluated in two published network meta-analyses. The proposed methodology is publicly available in an R package called ssifs, published on CRAN and developed and maintained by the authors of this work.

UNASSIGNED: Chinese medicine belly button application (CMBBA) has been used to treat childhood diarrhea (CD) in several randomized controlled trials (RCTs), but its effectiveness and combination strategy still need to be clarified. Therefore, we aimed to evaluate the effectiveness, safety, and the optimal combination strategy of CMBBA in treating CD.
UNASSIGNED: Up until January 2023, we searched for studies that met our inclusion criteria in six databases, including PubMed, the Cochrane Library, Chinese SinoMed, CNKI, VIP, and Wanfang. Heterogeneity was quantified using I2 statistics. A methodological evaluation was performed using the Cochrane Risk Bias Tool 2.0. The Confidence in Network Meta-Analysis online software was employed to evaluate evidence grading. A minimally contextualized framework was used to provide a comprehensive conclusion for the network meta-analysis. This study protocol was registered with PROSPERO.
UNASSIGNED: We analyzed data from 33 RCTs that included 4,490 children with diarrhea. In terms of clinical effectiveness, CMBBA plus montmorillonite powder plus anti-infectives may be the most effective treatment option for children with diarrhea and concurrent infection according to a minimally contextualized framework. Either exclusive use of CMBBA or CMBBA in combination with modern medicine was beneficial in reducing the time to diarrhea disappearance (MD = -1.33 days, 95% CI: -1.59 to -1.08, Z = -10.103, p < 0.001) compared to modern medicine exclusively, and the difference was statistically significant. The combined usage of CMBBA could shorten the recovery time of dehydration by an average of 0.74 days (MD = -0.74 days, 95% CI: -1.10 to -0.37, Z = -3.931.103, p < 0.001). While some studies have reported mild allergic reactions and mild abdominal pain after CMBBA use, these symptoms can be cured in a relatively short period of time.
UNASSIGNED: The combination of CMBBA, montmorillonite powder, and anti-infectives may provide superior clinical effectiveness for children with diarrhea and concurrent infection. To treat CD, CMBBA can be used effectively and safely. However, the findings must be interpreted with cautiously due to the limited number of clinical trials and the low quality of the studies. In addition, the choice of treatment plan should also be based on the specific conditions of each patient.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022380694.

BACKGROUND: Assisted reproductive technology (ART) has brought good news to infertile patients, but how to improve the pregnancy outcome of poor ovarian response (POR) patients is still a serious challenge and the scientific evidence of some adjuvant therapies remains controversial.
OBJECTIVE: Based on previous evidence, the purpose of this systematic review and network meta-analysis was to evaluate the effects of DHEA, CoQ10, GH and TEAS on pregnancy outcomes in POR patients undergoing in vitro fertilization and embryo transplantation (IVF-ET). In addition, we aimed to determine the current optimal adjuvant treatment strategies for POR.
METHODS: PubMed, Embase, The Cochrane Library and four databases in China (CNKI, Wanfang, VIP, SinoMed) were systematically searched up to July 30, 2022, with no restrictions on language. We included randomized controlled trials (RCTs) of adjuvant treatment strategies (DHEA, CoQ10, GH and TEAS) before IVF-ET to improve pregnancy outcomes in POR patients, while the control group received a controlled ovarian stimulation (COS) regimen only. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The surface under the cumulative ranking curve (SUCRA) was used to provide a pooled measure of cumulative ranking for each outcome.
RESULTS: Sixteen RCTs (2323 women) with POR defined using the Bologna criteria were included in the network meta-analysis. Compared with the control group, CoQ10 (OR 2.22, 95% CI: 1.05 to 4.71) and DHEA (OR 1.92, 95% CI: 1.16 to 3.16) had obvious advantages in improving the clinical pregnancy rate. CoQ10 was the best in improving the live birth rate (OR 2.36, 95% CI: 1.07 to 5.38). DHEA increased the embryo implantation rate (OR 2.80, 95%CI: 1.41 to 5.57) and the high-quality embryo rate (OR 2.01, 95% CI: 1.07 to 3.78) and number of oocytes retrieved (WMD 1.63, 95% CI: 0.34 to 2.92) showed a greater advantage, with GH in second place. Several adjuvant treatment strategies had no significant effect on reducing the cycle canceling rate compared with the control group. TEAS was the least effective of the four adjuvant treatments in most pooled results, but the overall effect appeared to be better than that of the control group.
CONCLUSIONS: Compared with COS regimen, the adjuvant use of CoQ10, DHEA and GH before IVF may have a better clinical effect on the pregnancy outcome of POR patients. TEAS needs careful consideration in improving the clinical pregnancy rate. Future large-scale RCTs with direct comparisons are needed to validate or update this conclusion.
BACKGROUND: PROSPERO CRD42022304723.

Classical normal mode analysis (cNMA) is a standard method for studying the equilibrium vibrations of macromolecules. A major limitation of cNMA is that it requires a cumbersome step of energy minimization that also alters the input structure significantly. Variants of normal mode analysis (NMA) exist that perform NMA directly on PDB structures without energy minimization, while maintaining most of the accuracy of cNMA. Spring-based NMA (sbNMA) is such a model. sbNMA uses an all-atom force field as cNMA does, which includes bonded terms such as bond stretching, bond angle bending, torsional, improper, and non-bonded terms such as van der Waals interactions. Electrostatics was not included in sbNMA because it introduced negative spring constants. In this work, we present a way to incorporate most of the electrostatic contributions in normal mode computations, which marks another significant step toward a free-energy-based elastic network model (ENM) for NMA. The vast majority of ENMs are entropy models. One significance of having a free energy-based model for NMA is that it allows one to study the contributions of both entropy and enthalpy. As an application, we apply this model to study the binding stability between SARS-COV2 and angiotensin converting enzyme 2 (or ACE2). Our results show that the stability at the binding interface is contributed nearly equally by hydrophobic interactions and hydrogen bonds.