bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel radiomics based on multi-parametric magnetic resonance imaging for predicting Ki-67 expression in rectal cancer: a multicenter study
Authors: Yao Xiuzhen , Ao Weiqun , Zhu Xiandi , Tian Shuyuan , Han Xiaoyu , Hu Jinwen , Xu Wenjie , Mao Guoqun , Deng Shuitang
Published: October 2023

Background

To explore the value of multiparametric MRI markers for preoperative prediction of Ki-67 expression among patients with rectal cancer.

Methods

Data from 259 patients with postoperative pathological confirmation of rectal adenocarcinoma who had received enhanced MRI and Ki-67 detection was divided into 4 cohorts: training (139 cases), internal validation (in-valid, 60 cases), and external validation (ex-valid, 60 cases) cohorts. The patients were divided into low and high Ki-67 expression groups. In the training cohort, DWI, T2WI, and contrast enhancement T1WI (CE-T1) sequence radiomics features were extracted from MRI images. Radiomics marker scores and regression coefficient were then calculated for data fitting to construct a radscore model. Subsequently, clinical features with statistical significance were selected to construct a combined model for preoperative individualized prediction of rectal cancer Ki-67 expression. The models were internally and externally validated, and the AUC of each model was calculated. Calibration and decision curves were used to evaluate the clinical practicality of nomograms.

Results

Three models for predicting rectal cancer Ki-67 expression were constructed. The AUC and Delong test results revealed that the combined model had better prediction performance than other models in three chohrts. A decision curve analysis revealed that the nomogram based on the combined model had relatively good clinical performance, which can be an intuitive prediction tool for clinicians.

Conclusion

The multiparametric MRI radiomics model can provide a noninvasive and accurate auxiliary tool for preoperative evaluation of Ki-67 expression in patients with rectal cancer and can support clinical decision-making.
Rehospitalisation rates after long-term follow-up of patients with severe mental illness admitted for more than one year: a systematic review
Authors: Sato Sayaka , Nakanishi Miharu , Ogawa Makoto , Abe Makiko , Yasuma Naonori , Kono Toshiaki , Igarashi Momoka , Iwanaga Mai , Kawaguchi Takayuki , Yamaguchi Sosei
Published: October 2023

Aims

This study aimed to conduct a systematic review of studies on the outcomes of long-term hospitalisation of individuals with severe mental illness, considering readmission rates as the primary outcome.

Methods

Studies considered were those in which participants were aged between 18 and 64 years with severe mental illness; exposure to psychiatric hospitals or wards was long-term (more than one year); primary outcomes were readmission rates; secondary outcomes were duration of readmission, employment, schooling, and social participation; and the study design was either observational or interventional with a randomised controlled trial (RCT) design. Relevant studies were searched using MEDLINE, PsycINFO, Web of Science, CINAHL, and the Japan Medical Abstract Society. The final search was conducted on 1 February 2022. The risk of bias in non-randomised studies of interventions was used to assess the methodological quality. A descriptive literature review is also conducted.

Results

Of the 11,999 studies initially searched, three cohort studies (2,293 participants) met the eligibility criteria. The risk of bias in these studies was rated as critical or serious. The 1–10 years readmission rate for patients with schizophrenia who had been hospitalised for more than one year ranged from 33 to 55%. The average of readmission durations described in the two studies was 70.5 ± 95.6 days per year (in the case of a 7.5-year follow-up) and 306 ± 399 days (in the case of a 3–8-year follow-up). None of the studies reported other outcomes defined in this study.

Conclusions

The readmission rates in the included studies varied. Differences in the follow-up period or the intensity of community services may have contributed to this variability. In countries preparing to implement de-institutionalisation, highly individualised community support should be designed to avoid relocation to residential services under supervision. The length of stay for readmissions was shorter than that for index admissions. The results also imply that discharge to the community contributes to improved clinical outcomes such as improved social functioning. The validity of retaining patients admitted because of the risk of rehospitalisation was considered low. Future research directions have also been discussed.
Hypertension care cascade in an urban resettlement colony and slum in Delhi, India: a cross-sectional survey
Authors: Singh Mongjam Meghachandra , Basu Saurav , Lalwani Heena , Rao Shivani , Maheshwari Vansh , Garg Sandeep , Sharma Nandini
Published: October 2023

Background

Hypertension care cascade in resource-limited settings is compromised with a majority of patients with hypertension remaining undiagnosed, untreated, non-adherent, and poorly controlled at every stage. However, there is paucity of information on care and management of hypertensive patients in community-based settings of low-income urban neighbourhoods in India.

Methods

This was a community-based cross-sectional study conducted in an urban resettlement colony and slum area in the Northeast District of Delhi. The adult population was screened for hypertension using standardized methods, and adherence to medications was assessed using the Morisky Green Levine scale. Binary logistic regression analysis was conducted to ascertain the sociodemographic predictors of the outcome (presence of hypertension, adherence to antihypertensive medication, blood pressure control). A p-value < 0.05 was considered statistically significant.

Results

We included 8850 adult participants including 5295 females and 3555 males in this study. Nearly 29% of the participants were hypertensive, of which 61.77% were newly diagnosed cases. Furthermore, nearly 81% of the previously diagnosed cases had been initiated on antihypertensive medication, of which 57.54% were adherent to their medications while 36.12% attained controlled blood pressure levels. The odds of having hypertension were significantly higher among males (AOR = 1.87, 95% CI: 1.63 to 2.15), age ≥ 60 years (AOR = 9.15, 95% CI: 7.82 to 10.70), high waist circumference (AOR = 2.24, 95% CI: 1.86 to 2.70) and Body Mass Index of ≥ 25.00 (AOR = 2.55, 95% CI: 2.00 to 3.26). Furthermore, on adjusted analysis, patients of hypertension having diabetes (DM) comorbidity had significantly higher odds of being adherent to anti-hypertensive medications (AOR = 1.81, 95% CI: 1.31 to 2.51) compared to those without DM comorbidity, while tobacco users had significantly lower odds of being adherent to antihypertensive medication (AOR = 0.50, 95% CI: 0.31 to 0.82).

Conclusions

Hypertension care cascade in urban slum-resettlement colony setting revealed a high burden of undiagnosed hypertension, low rates of medication adherence, and poor blood pressure control. Strengthening community screening and primary care continuum of care is necessary to improve the hypertension care cascade from early diagnosis to effective management with optimal health outcomes to reduce patient complications and increase longevity.
Resting heart rate and the risk of incident type 2 diabetes mellitus among non-diabetic and prediabetic Iranian adults: Tehran lipid and glucose study
Authors: Moazzeni Seyyed Saeed , Karimi Toudeshki Kimia , Ghorbanpouryami Fatemeh , Hasheminia Mitra , Azizi Fereidoun , Pishgahi Mehdi , Hadaegh Farzad
Published: October 2023

Background

Resting heart rate (RHR) has been found to be a potential risk factor for developing type 2 diabetes mellitus (T2DM), with a highly significant heterogeneity among previous studies. Therefore, we examined the association of RHR and risk of incident T2DM among non-diabetic and prediabetic adults.

Methods

The study population included 2431 men and 2910 women aged ≥ 20 years without T2DM at baseline (2001–2005). Participants were followed for incident T2DM by about 3-year intervals up to April 2018. The multivariable Cox proportional models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The models were adjusted for age, body mass index, waist circumference, educational level, physical activity, smoking, hypertension, family history of diabetes, triglycerides/ high-density lipoprotein cholesterol ratio, and fasting plasma glucose.

Results

During a median follow-up of 12.2 years, 313 men and 375 women developed T2DM. Interestingly, a significant sex-difference was found (all P-values for sex interaction < 0.025). Among men, compared to the first quintile (< 68 bpm: beats per minute), those who had RHR of over 84 bpm were at higher T2DM risk with a HR (95%CI) of 1.69 (1.16–2.47). Furthermore, considering RHR as a continuous variable, an increase of 10 bpm caused 17% significantly higher risk among men with a HR of 1.17 (1.05–1.30). However, among women, there was no significant association between incident T2DM and RHR. Moreover, among prediabetic participants at baseline, the association of RHR and risk of T2DM progression was generally similar to the general population, which means higher RHR increased the risk of T2DM development only among men with a HR of 1.26 (1.09–1.46) for 10 bpm increase.

Conclusions

Among men, being either non-diabetic or prediabetic at baseline, higher RHR can be associated with incident T2DM; however, women didn’t show a significant association. Further studies are needed to determine the added value of RHR as a potential modifiable risk factor in screening and risk prediction of incident T2DM.
Hook plate fixation of Neer type II distal clavicle fractures results in satisfactory patient-reported outcomes but complications and revisions are high
Authors: Beisemann Nils , Spiller Yannik M. , Schnetzke Marc , Grützner Paul Alfred , Nolte Philip-Christian
Published: October 2023

Background

Surgical treatment of distal clavicle fractures Neer type II is challenging. A gold standard has not yet been established, thus various surgical procedures have been described. The purpose of this study is to report the radiological and clinical outcomes using hook plate fixation in Neer type II distal clavicle fractures.

Methods

We retrospectively reviewed data of 53 patients who underwent hook plate fixation between December 2009 and December 2019 with ≥ 2 years of follow-up. Patients with preexisting pathologies or concomitant injuries of the ipsilateral shoulder were excluded. Pre- and postoperative coracoclavicular distance (CCD), bony union and patient-reported outcomes were collected, including the Constant Score (CS) and Subjective Shoulder Value (SSV). Complications and revisions were recorded.

Results

At a mean final follow-up of 6.2 years, mean SSV was 91.0% (range, 20–100) and mean CS was 80.9 points (range, 25–99). The mean preoperative CCD was 19.0 mm (range, 5.7–31.8), the mean postoperative CCD was 8.2 mm (range, 4.4–12.2) and the mean CCD following hardware removal was 9.7 mm (range, 4.7–18.8). The loss of reduction following hardware removal was statistically significant (P = 0.007). Eleven (20.8%) patients had complications, with 5 cases of deep or superficial infection (9.4%), four non-unions (7.5%), one periosteosynthetic fracture, one postoperative seroma, one implant failure and one symptomatic acromioclavicular joint arthritis (all 1.9%). A total of 10 patients (18.9%) underwent revision surgery at a mean of 113 (range, 7–631) days.

Conclusion

Medium-term patient-reported outcomes for hook plate fixation of Neer type II distal clavicle fractures are satisfactory; however, one in five patients suffers a complication with the majority of them requiring revision surgery.
Ceph-Net: automatic detection of cephalometric landmarks on scanned lateral cephalograms from children and adolescents using an attention-based stacked regression network
Authors: Yang Su , Song Eun Sun , Lee Eun Seung , Kang Se-Ryong , Yi Won-Jin , Lee Seung-Pyo
Published: October 2023

Background

The success of cephalometric analysis depends on the accurate detection of cephalometric landmarks on scanned lateral cephalograms. However, manual cephalometric analysis is time-consuming and can cause inter- and intra-observer variability. The purpose of this study was to automatically detect cephalometric landmarks on scanned lateral cephalograms with low contrast and resolution using an attention-based stacked regression network (Ceph-Net).

Methods

The main body of Ceph-Net compromised stacked fully convolutional networks (FCN) which progressively refined the detection of cephalometric landmarks on each FCN. By embedding dual attention and multi-path convolution modules in Ceph-Net, the network learned local and global context and semantic relationships between cephalometric landmarks. Additionally, the intermediate deep supervision in each FCN further boosted the training stability and the detection performance of cephalometric landmarks.

Results

Ceph-Net showed a superior detection performance in mean radial error and successful detection rate, including accuracy improvements in cephalometric landmark detection located in low-contrast soft tissues compared with other detection networks. Moreover, Ceph-Net presented superior detection performance on the test dataset split by age from 8 to 16 years old.

Conclusions

Ceph-Net demonstrated an automatic and superior detection of cephalometric landmarks by successfully learning local and global context and semantic relationships between cephalometric landmarks in scanned lateral cephalograms with low contrast and resolutions.
Should IUI replace IVF as first-line treatment for unexplained infertility? A literature review
Authors: Man Jessica Ka-Yan , Parker Anne Elizabeth , Broughton Sophie , Ikhlaq Hamza , Das Mausumi
Published: October 2023

Background

Unexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation (IVF), are often sought. Despite the National Institute for Health and Care Excellence (NICE) recommending IVF for unexplained infertility, this recommendation has generated an ongoing debate, with few fertility clinics discontinuing the use of IUI as the first-line management of choice. In contrast to NICE, recent guidance released from the European Society for Human Reproduction and Embryology (ESHRE) in August 2023 supports the use of IUI as first-line. High-quality evidence behind such interventions is lacking, with current literature providing conflicting results.

Aims

This review aims to provide a literature overview exploring whether IUI or IVF should be used as first-line treatment for couples with unexplained infertility, in the context of current guidelines.

Methods

The primary outcome used to assess efficacy of both treatment methods is live birth (LB) rates. Secondary outcomes used are clinical pregnancy (CP) and ongoing pregnancy (OP) rates. A comprehensive literature search of 4 databases: Ovid MEDLINE, EMBASE, Maternity & Infant Care and the Cochrane Library were searched in January 2022. Upon removal of duplications, abstract screening, and full-text screening, a total of 34 papers were selected.

Discussion/conclusion

This review highlights a large discrepancy in the literature when examining pregnancy outcomes of IUI and IVF treatments. Evidence shows IUI increases LB and CP rates 3-fold compared to expectant management. Literature comparing IUI to IVF is less certain. The review finds the literature implies IVF should be used for first-line management but the paucity of high-quality randomised controlled trials (RCTs), coupled with heterogeneity of the identified studies and a lack of research amongst women > 40 years warrants the need for further large RCTs. The decision to offer IUI with ovarian stimulation (IUI-OS) or IVF should be based upon patient prognostic factors. We suggest that IUI-OS could be offered as first-line treatment for unexplained infertility for women < 38 years, with good prognosis, and IVF could be offered first to those > 38 years. Patients should be appropriately counselled to enable informed decision making.
Acupuncture versus sham acupuncture and usual care for Antiandrogen-Induced hot fLashes in prostate cancer (AVAIL): study protocol for a randomized clinical trial
Authors: Qin Zongshi , Zang Zhiwei , Yu Jianyong , Lv Jianqin , Li Ning , Zhang Jialing , Yang Mingxiao , Kwong Joey S. W. , Pang Ran , Wang Jianfeng , Cui Zhengyu , Yu Yongpei , Wang Haibo , Zhu Yidan , Yuan Yifang , Li Xiao , Wu Yangfeng , Wu Jiani
Published: October 2023

Background

Hot flashes are the common and debilitating symptom among prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Strong evidence from multiple rigorously designed studies indicated that pharmacological option such as venlafaxine provides partial relief, but the tolerability is poor when dose is not tapered. Hence, alternative therapy is needed. Previous studies reported that acupuncture may be helpful in the management of hot flashes. However, the insufficient randomized controlled trial limited the quality of evidence.

Methods

Five hospitals will recruit 120 acupuncture naïve patients with moderate-to-severe hot flashes after prostate cancer received ADT in China from February 2023 to December 2024. Participants will be randomly 2:1:1 allocated to the 18 sessions of verum acupuncture at true acupuncture points plus usual care, 18 sessions of non-penetrating sham acupuncture at non-acupuncture points plus usual care, or usual care alone over 6 weeks. The primary outcome measure is the change of mean weekly hot flashes symptom severity score (HFSSS) at the end of treatment compared with baseline.

Expected Results and Conclusion

We will be able to measure the effectiveness of acupuncture for patients with PCa suffering from ADT-induced hot flashes and whether acupuncture is superior to sham acupuncture and usual care. The proposed acupuncture treatment might provide an alternative option for those patients.

Trial Registration

Clinicaltrials.gov (NCT05069467).
Analysis of ethical considerations of COVID‑19 vaccination: lessons for future
Authors: Malekzadeh Roya , Abedi Ghasem , Ziapour Arash , Yıldırım Murat , Amirkhanlou Afshin
Published: October 2023

Background

Since the beginning of the COVID-19 pandemic, different countries sought to manufacture and supply effective vaccines to control the disease and prevent and protect public health in society. The implementation of vaccination has created many ethical dilemmas for humans, which must be recognized and resolved. Therefore, the present study was conducted to analyze the ethical considerations in vaccination against COVID-19 from the perspective of service providers.

Methods

The present qualitative research was conducted in 2022 in the north of Iran. The participants included 23 health workers with at least five years of work experience and members of the COVID-19 vaccination team. The data were initially collected through systematic semi-structured interviews, then snowball sampling and finally continued until data saturation. The next steps were transcription of interviews, identification of meaning units, coding, categorization based on similarity and symmetry, extraction of themes and the analysis of themes through content analysis.

Results

The analysis of participants’ experiences led to the extraction of five main categories of themes and fifteen sub-categories of the ethical considerations of COVID-19 vaccination. Safe and standard vaccine production, vaccine supply, fairness, respect for autonomy, and accountability were the main categories. The subcategories included compliance with scientific and ethical procedures, effectiveness and profitability of vaccine, absence of severe adverse effects, allocation of resources for vaccine supply, vaccine availability, diversity and comprehensiveness of alternative vaccines, vaccination prioritization, prioritization of the vulnerable populations of society, autonomy of patient (equal rights), autonomy of community, autonomy of service providers, reporting correct information, reporting vaccine side effects, public trust and acceptance.

Conclusion

The health system managers should be adequately prepared to solve the ethical problems posed by COVID-19 vaccination. Therefore, it is recommended to avoid haste in vaccination and pay more attention to vaccination safety standards, provide sufficient resources for a comprehensive vaccine supply, pay close attention to collective interests versus individual interests, and meet community needs.
Job demand and job resource factors explaining stress and job satisfaction among home care nurses – a mixed-methods sequential explanatory study
Authors: Kaihlanen Anu-Marja , Ruotsalainen Salla , Väisänen Visa , Corneliusson Laura , Pesonen Tiina , Sinervo Timo
Published: October 2023

Background

Increasing home care has been seen as a way to respond to the growing care needs of the aging population. To secure a sufficient number of nurses to provide home care, it is essential to identify and take into account the factors related to their well-being and job satisfaction. This study examined associations of both objective and subjective job demands and resources with stress and job satisfaction among nurses working in home care.

Methods

This study used a mixed-methods sequential explanatory design. First, quantitative data was collected with a survey, followed by a qualitative survey with open-ended questions. Linear regression analyses and qualitative content analysis with an inductive approach were used to analyze the quantitative and qualitative data, respectively. Joint display in a form of a table was used to integrate the results.

Results

Of the objectively measured job demands and resources, higher proportion of direct care time and higher number of interruptions were associated with higher stress in the fully adjusted models. Of the subjective measures, higher time pressure, role conflicts and disruptions were associated with higher stress. Higher time pressure, role conflicts, and disruptions in the workday were associated with lower job satisfaction, whereas higher care continuity and having more autonomy were associated with higher job satisfaction. The results of the qualitative study, in which the nurses described their experiences of their working week, partly explained and confirmed the results of the quantitative study but were also contradictory in some respects.

Conclusions

Many demands, both subjectively experienced and objectively measured in terms of work organization, may undermine home care nurses’ well-being and enjoyment at work. A severe nursing shortage combined with a growing number of clients is the reality of home care, significantly increasing the risk of burnout and turnover among employees. Strategies must be developed urgently to ensure sufficient personnel in home care. For example, investments should be made in opportunities for autonomous planning of work, and promotion of good cooperation and functionality of work teams.
Klotho inhibits renal ox-LDL deposition via IGF-1R/RAC1/OLR1 signaling to ameliorate podocyte injury in diabetic kidney disease
Authors: Jiang Wei , Gan Chun , Zhou Xindi , Yang Qing , Chen Dan , Xiao Han , Dai Lujun , Chen Yaxi , Wang Mo , Yang Haiping , Li Qiu
Published: October 2023

Objective

Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation.

Methods

We conducted a comprehensive analysis of serum and kidney biopsy samples obtained from patients diagnosed with DKD. Additionally, to explore the underlying mechanism of Klotho in the deposition of ox-LDL in the kidneys, we employed a mouse model of DKD with the Klotho genotype induced by streptozotocin (STZ). Furthermore, we conducted meticulous in vitro experiments on podocytes to gain further insights into the specific role of Klotho in the deposition of ox-LDL within the kidney.

Results

Our groundbreaking study unveiled the remarkable ability of the soluble form of Klotho to effectively inhibit high glucose-induced ox-LDL deposition in podocytes affected by DKD. Subsequent investigations elucidated that Klotho achieved this inhibition by reducing the expression of the insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading to a decrease in the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) and an enhancement of mitochondrial function. Ultimately, this series of events culminated in a significant reduction in the expression of the oxidized low-density lipoprotein receptor (OLR1), thereby resulting in a notable decrease in renal ox-LDL deposition in DKD.

Conclusion

Our findings suggested that Klotho had the potential to mitigate podocyte injury and reduced high glucose-induced ox-LDL deposition in glomerulus by modulating the IGF-1R/RAC1/OLR1 signaling. These results provided valuable insights that could inform the development of novel strategies for diagnosing and treating DKD.

Graphical Abstract
Triglyceride-glucose index is associated with poor prognosis in acute coronary syndrome patients with prior coronary artery bypass grafting undergoing percutaneous coronary intervention
Authors: Dong Shutong , Zhao Zehao , Huang Xin , Ma Meishi , Yang Zhiqiang , Fan Chu , Han Hongya , Wang Zhijian , Shi Dongmei , Zhou Yujie
Published: October 2023

Background

The triglyceride-glucose (TyG) index, which is a reliable substitute indicator for insulin resistance, has been considered an independent risk factor for long-term outcomes in patients with cardiovascular disease. However, it remains unknown whether the TyG index is associated with poor prognosis in acute coronary syndrome (ACS) patients with prior coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI).

Methods

A total of 1158 ACS patients with prior CABG undergoing PCI were retrospectively studied. The TyG index was calculated by ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization.

Results

During a median of 42-month follow-up, 350 patients (30.2%) experienced at least one endpoint event. Based on the optimal cut-off value of the TyG index, patients were divided into the high TyG index group and the low TyG index group. Patients in the high TyG index group had higher risks of MACCE (35.3% vs. 25.3%, p < 0.001), major adverse cardiovascular events (MACE) (31.1% vs. 23.4%, p = 0.003), nonfatal stroke (4.2% vs. 1.9%, p = 0.022) and unplanned repeat revascularization (19.4% vs. 11.3%, p < 0.001) than those in the low TyG index group. Cox regression analysis demonstrated that there was an independent association between the TyG index and MACCE regardless of whether the TyG index was a continuous or categorical variable (HR 1.42, 95% CI 1.09–1.86, p = 0.009; HR 1.53, 95% CI 1.16–2.01, p = 0.003, respectively). Restricted cubic spline curve exhibited that the relationship between the TyG index and MACCE was linear (p for non-linear = 0.595, p for overall = 0.005). By incorporating the TyG index groups into baseline risk model, the accuracy of predicting MACCE was improved [AUC: baseline risk model, 0.618 vs. baseline risk model + TyG index groups, 0.636, p for comparison = 0.042].

Conclusions

The TyG index is independently associated with MACCE, suggesting that the TyG index may serve as a valid indicator for predicting poor prognosis in ACS patients with prior CABG undergoing PCI.
Impact of SGLT2 inhibitors on patient outcomes: a network meta-analysis
Authors: Chen Jui-Yi , Pan Heng-Chih , Shiao Chih-Chung , Chuang Min-Hsiang , See Chun Yin , Yeh Tzu-Hsuan , Yang Yafei , Chu Wen-Kai , Wu Vin-Cent
Published: October 2023

Background

A comprehensive network meta-analysis comparing the effects of individual sodium-glucose cotransporter 2 (SGLT2) inhibitors on patients with and without comorbidities including diabetes mellitus (DM), heart failure (HF), and chronic kidney disease (CKD) has not been previously conducted.

Methods

We searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for randomized controlled trials up to March 28, 2023. Network meta-analysis using a random-effects model was conducted to calculate risk ratios (RRs). Risk of Bias tool 2.0 was used to assess bias, and CINeMA to assess the certainty of evidence. In the subgroup analysis, the SGLT2 inhibitors were classified into highly (dapagliflozin, empagliflozin, and ertugliflozin) and less selective SGLT2 inhibitors (canagliflozin and sotagliflozin).

Results

A total of fourteen trials with 75,334 patients were analyzed. Among these, 40,956 had taken SGLT2 inhibitors and 34,378 had not. One of the main results with particular findings was empagliflozin users had a significantly lower risk of all-cause death compared to dapagliflozin users in DM population (RR: 0.81, 95% CI 0.69–0.96). In HF population, sotagliflozin users had a borderline significantly lower risk of CV death or hospitalization for HF (HHF) than dapagliflozin users (RR: 0.90, 95% CI 0.80–1.01). In non-HF population, those who used canagliflozin had a significantly lower risk of CV death or HHF compared with those who used dapagliflozin (RR: 0.75, 95% CI 0.58–0.98). At last, for HF patients, those who used less selective SGLT2 inhibitors had a significantly lower risk of MACEs compared to those who used highly selective SGLT2 inhibitors (RR: 0.75, 95% CI 0.62–0.90).

Conclusions

Our network meta-analysis revealed that empagliflozin users with diabetes experienced a lower risk of dying from any cause than those using dapagliflozin. Additionally, canagliflozin users demonstrated a reduced risk of cardiovascular death or HHF compared to dapagliflozin users in those without HF. In HF patients, less selective SGLT2 inhibitors showed superior CV composite outcomes, even surpassing the performance of highly selective SGLT2 inhibitors.

Trial registration: PROSPERO [CRD42022361906].
Clinical evaluation of metagenomic next-generation sequencing in unbiased pathogen diagnosis of urinary tract infection
Authors: Wang Ye , Chen Ting , Zhang Shengwei , Zhang Lei , Li Qian , Lv Qingyu , Kong Decong , Jiang Hua , Ren Yuhao , Jiang Yongqiang , Li Yan , Huang Wenhua , Liu Peng
Published: October 2023

Background

Early availability of pathogen identification in urinary tract infections (UTIs) has critical importance in disease management. Metagenomic next-generation sequencing (mNGS) has the potential to transform how acute and serious infections are diagnosed by offering unbiased and culture-free pathogen detection. However, clinical experience with application of the mNGS test is relatively limited.

Methods

We therefore established a MinION-based mNGS pathogens diagnostic platform and evaluated its potential for clinical implementation in UTIs with clinical samples. 213 urine samples from patients with suspected UTIs were included and subjected to mNGS testing using the MinION platform. mNGS results were compared to the gold standard of clinical culture and composite standard of combining clinical testing, confirmatory qPCR testing, and clinical adjudication by doctors.

Results

The mNGS exhibited a sensitivity of 81.4% and a specificity of 92.3%, along with a positive predictive value of 96.6%, a negative predictive value of 64.9%, and an overall accuracy of 84.4%, all of which were determined based on the gold standard of routine culture results. When assessed against the composite standard, the sensitivity and specificity both increased to 89.9% and 100%, respectively, while the accuracy rose to 92.4%. Notably, the positive predictive value and negative predictive value also saw improvements, reaching 100% and 76.8%, respectively. Moreover, this diagnostic platform successfully identified dsDNA viruses. Among the 65 culture-negative samples, the viral detection rate reached 33.8% (22/65) and was subsequently validated through qPCR. Furthermore, the automatic bioinformatics pipeline we developed enabled one-click analysis from data to results, leading to a significant reduction in diagnosis time.

Conclusion

These results demonstrate that the pathogen detection performance of mNGS is sufficient for diagnostic testing in clinical settings. As the method is generally unbiased, it can improve diagnostic testing of UTIs and other microbial infections.
Integration of machine learning to identify diagnostic genes in leukocytes for acute myocardial infarction patients
Authors: Zhang Lin , Liu Yue , Wang Kaiyue , Ou Xiangqin , Zhou Jiashun , Zhang Houliang , Huang Min , Du Zhenfang , Qiang Sheng
Published: October 2023

Background

Acute myocardial infarction (AMI) has two clinical characteristics: high missed diagnosis and dysfunction of leukocytes. Transcriptional RNA on leukocytes is closely related to the course evolution of AMI patients. We hypothesized that transcriptional RNA in leukocytes might provide potential diagnostic value for AMI. Integration machine learning (IML) was first used to explore AMI discrimination genes. The following clinical study was performed to validate the results.

Methods

A total of four AMI microarrays (derived from the Gene Expression Omnibus) were included in bioanalysis (220 sample size). Then, the clinical validation was finished with 20 AMI and 20 stable coronary artery disease patients (SCAD). At a ratio of 5:2, GSE59867 was included in the training set, while GSE60993, GSE62646, and GSE48060 were included in the testing set. IML was explicitly proposed in this research, which is composed of six machine learning algorithms, including support vector machine (SVM), neural network (NN), random forest (RF), gradient boosting machine (GBM), decision trees (DT), and least absolute shrinkage and selection operator (LASSO). IML had two functions in this research: filtered optimized variables and predicted the categorized value. Finally, The RNA of the recruited patients was analyzed to verify the results of IML.

Results

Thirty-nine differentially expressed genes (DEGs) were identified between controls and AMI individuals from the training sets. Among the thirty-nine DEGs, IML was used to process the predicted classification model and identify potential candidate genes with overall normalized weights > 1. Finally, two genes (AQP9 and SOCS3) show their diagnosis value with the area under the curve (AUC) > 0.9 in both the training and testing sets. The clinical study verified the significance of AQP9 and SOCS3. Notably, more stenotic coronary arteries or severe Killip classification indicated higher levels of these two genes, especially SOCS3. These two genes correlated with two immune cell types, monocytes and neutrophils.

Conclusion

AQP9 and SOCS3 in leukocytes may be conducive to identifying AMI patients with SCAD patients. AQP9 and SOCS3 are closely associated with monocytes and neutrophils, which might contribute to advancing AMI diagnosis and shed light on novel genetic markers. Multiple clinical characteristics, multicenter, and large-sample relevant trials are still needed to confirm its clinical value.
Spatiotemporal evolution of AML immune microenvironment remodeling and RNF149-driven drug resistance through single-cell multidimensional analysis
Authors: Wu Xin , Wu Zhongguang , Deng Woding , Xu Rong , Ban Chunmei , Sun Xiaoying , Zhao Qiangqiang
Published: October 2023

Background

The composition of the bone marrow immune microenvironment in patients with acute myeloid leukaemia (AML) was analysed by single-cell sequencing and the evolutionary role of different subpopulations of T cells in the development of AML and in driving drug resistance was explored in conjunction with E3 ubiquitin ligase-related genes.

Methods

To elucidate the mechanisms underlying AML-NR and Ara-C resistance, we analyzed the bone marrow immune microenvironment of AML patients by integrating multiple single-cell RNA sequencing datasets. When compared to the AML disease remission (AML-CR) cohort, AML-NR displayed distinct cellular interactions and alterations in the ratios of CD4+T, Treg, and CD8+T cell populations.

Results

Our findings indicate that the E3 ubiquitin ligase RNF149 accelerates AML progression, modifies the AML immune milieu, triggers CD8+T cell dysfunction, and influences the transformation of CD8+ Navie.T cells to CD8+TExh, culminating in diminished AML responsiveness to chemotherapeutic agents. Experiments both in vivo and in vitro revealed RNF149’s role in enhancing AML drug-resistant cell line proliferation and in apoptotic inhibition, fostering resistance to Ara-C.

Conclusion

In essence, the immune microenvironments of AML-CR and AML-NR diverge considerably, spotlighting RNF149’s tumorigenic function in AML and cementing its status as a potential prognostic indicator and innovative therapeutic avenue for countering AML resistance.

Graphical Abstract
Cost-effective 3D scanning and printing technologies for outer ear reconstruction: current status
Authors: Wersényi György , Scheper Verena , Spagnol Simone , Eixelberger Thomas , Wittenberg Thomas
Published: October 2023

Current 3D scanning and printing technologies offer not only state-of-the-art developments in the field of medical imaging and bio-engineering, but also cost and time effective solutions for surgical reconstruction procedures. Besides tissue engineering, where living cells are used, bio-compatible polymers or synthetic resin can be applied. The combination of 3D handheld scanning devices or volumetric imaging, (open-source) image processing packages, and 3D printers form a complete workflow chain that is capable of effective rapid prototyping of outer ear replicas. This paper reviews current possibilities and latest use cases for 3D-scanning, data processing and printing of outer ear replicas with a focus on low-cost solutions for rehabilitation engineering.
Concomitant malnutrition and frailty are significant risk factors for poor outcome following two-stage revision for chronic periprosthetic joint infection
Authors: Shi Tengbin , Chen Zhi , Hu Dingxiang , Wu Dingwei , Wang Zhenyu , Liu Wenge
Published: October 2023

Background

Two-stage revision remains the gold standard for periprosthetic joint infection (PJI) treatment. Although previous studies have examined malnutrition and frailty independently, their cumulative effects are not clear. Therefore, this study aimed to assess the individual and combined influence of malnutrition and frailty on the two-stage revision surgery.

Methods

Patients with chronic PJI undergoing two-stage revision were retrospectively included. The definition of PJI is completely consistent with the evidence-based definition of PJI recorded by the MSIS in 2018. Preoperative serum albumin levels and 11-item modified frailty index scores were collected. Four cohorts were created: (1) Normal (N), (2) Frail (F), (3) Malnourished (M), and (4) Malnourished and frail (MF). Demographic data, comorbidities, and postoperative complications were collected and compared between the four cohorts.

Results

A total of 117 consecutive patients were enrolled, 48% of patients were healthy (27.4% F, 16.2% M, and 9.4% MF). MF group showed lower scores on the physical composite scale of the 12-item short-form health survey (SF12-PCS), mental composite summary (SF12-MCS), Harris hip score (HHS), and knee society score (KSS) (P < 0.05). The incidence of reinfection in the MF group was higher than that in all other groups (MF vs. N; odds ratio [OR] 3.7, 95% confidence interval [CI] 1.37 − 8.82, P = 0.032). The incidence of complications in the MF group was higher than that in all other groups (MF vs. N; OR 4.81, 95% CI 1.58–9.26, P = 0.018). Postoperative transfusion events (OR 2.92, 95% CI 1.27–3.09, P = 0.021), readmission at 60 days after the operation (OR 4.91, 95% CI 1.82–13.80, P = 0.012) was higher in the MF patients. In addition, the extended length of stay after the operation was highest in the MF patients, with an OR of 5.78 (95% CI 2.16–12.04, P = 0.003).

Conclusion

The concurrent presence of concomitant malnutrition and frailty in patients with PJI is related to poor prognosis and may be a predictor of the efficacy of two-stage revision. Future research will be needed to describe the benefits of improving these risk factors for patients with PJI.
Case report: video-assisted thoracoscopic surgery for pulmonary arteriovenous malformation using near-infrared fluorescence with indocyanine green
Authors: Han Tianxiao , Gao Jian , Wang Zhenfan , Zhou Jian
Published: October 2023

Background

Pulmonary arteriovenous malformation (PAVM) is an abnormal communication between pulmonary vasculatures and has an unclear boundary with surrounding lung tissues. At present, surgeons can only determine its location by preoperative imaging and intraoperative palpation, despite its soft texture. Indocyanine green(ICG), a near-infrared fluorophore, has been demonstrated useful in the accurate identification of vascular tissue. Therefore, we explored its application in PAVM cases.

Case presentation

We present two PAVM cases using near-infrared fluorescence (NIF) with 25 mg ICG at 5 mg/ml to achieve intraoperative visualization of the lesion in video-assisted thoracoscopic surgery (VATS). Under the NIF mode, ICG systemic injection led to successive signaling of the anomaly and normal tissues in merely 10 s, which helped us distinguish them efficiently and precisely. A peak signal-to-background ratio of 2.2 confirmed the significant fluorescence difference and excluded interference from carbon dust.

Conclusions

We are the first to report the use of such an approach in delineating the margin of vascular malformation with high contrast, and this new finding may help minimize the damage to lung function in PAVM treatment. Further exploration and validation are needed to determine its role.
Discovery of novel 2,3,4,5-tetrahydrospiro[benzo[c]azepine-1,1’-cyclohexan]-5-ol derivatives as PARP-1 inhibitors
Authors: Yu Ling , Li Jian-hui , Zhu Ju , Wang You-de , Yan Zhi-wei , Zhang Li-ying , Li Shuai
Published: October 2023

As an essential marker of cancer treatment, PARP-1 inhibitors could effectively kill tumor cells through a mechanism known as synthetic lethality and are used to treat a variety of cancers. In order to explore novel PARP-1 inhibitors, a series of 22 novel erythrina derivatives were reported and preliminarily explored their mechanism of action. The antitumor activities against four human cancer cell lines including A549, OVCAR-3, HCT-116, and MCF-7 were evaluated, and the preliminary SARs were summarized. Among them, compound 11b exhibited better anti-proliferative effects against A549 cells (IC50 = 1.95 µM). The SI results showed that compound 11b had low toxicity. Moreover, compound 11b displayed excellent PARP-1 inhibitory activities with IC50 values of 19.24 nM. In addition, molecular docking studies provided the rational binding modes of compound 11b in complexes with PARP-1. The flow cytometry assays revealed that compound 11b could induce apoptosis of A549 cells (P < 0.001). Simultaneously, compound 11b could effectively reduce the formation of PAR (P < 0.001). The ADMET prediction results indicated compound 11b had similar properties to rucaparib. Collectively, compound 11b has potential research value for further investigation.
Aon: a service to augment Alliance Genome Resource data with additional species
Authors: Kearney Sophie K. , Berger Alexander , Baker Erich
Published: October 2023

Objective

Cross-species comparative genomics requires access to accurate homology data across the entire range of annotated genes. The Alliance of Genome Resources (AGR) provides an open-source and comprehensive database of homology data calculated using a wide array of algorithms at differing stringencies to elucidate orthologous relationships. However, the current AGR application program interface (API) is limited to five homology endpoints for nine species. While AGR provides a robust resource for several canonical species, its utility can be greatly enhanced by increased filtering and data processing options and incorporating additional species.

Results

Here, we describe a novel API tool, AON, that expands access to the AGR orthology resource by creating a data structure that supports 50 additional endpoints. More importantly, it provides users with a framework for adding bespoke endpoints, custom species, and additional orthology data. We demonstrate AON’s functionality by incorporating the service into the GeneWeaver ecosystem for supporting cross-species data analysis.
PEERNaija—a mobile health platform incentivizing medication adherence among youth living with HIV in Nigeria: study protocol for a randomized controlled trial
Authors: Pierce Leslie J. , Were Martin C. , Amaral Sandra , Aliyu Muktar H. , Ezechi Oliver , David Agatha , Idigbe Ifeoma , Musa Adesola Z. , Okonkwo Prosper , Dowshen Nadia , Ahonkhai Aima A.
Published: October 2023

Background

Poor medication adherence is a major barrier to HIV control among youth living with HIV (Y-PLWH). The PEERNaija application (app) is an adapted smartphone app grounded in social cognitive and contigency management theories and designed to harness peer-based social incentives and conditional financial incentives to promote medication adherence. The app delivers a multifaceted medication adherence intervention including (1) peer-based social incentives, (2) financial incentives, (3) virtual peer social support, and (4) early clinic-based outreach for non-adherent Y-PLWH. A pilot trial of the app will be conducted in Nigeria, Africa’s most populous country with the 4th largest HIV epidemic, and home to 10% of the world’s four million Y-PLWH.

Methods

In this randomized controlled trial, we will compare implementation outcomes (feasibility, acceptability, appropriateness measured via validated scales, enrollment and application installation rates, feedback surveys and focus group discussions with participants, and back-end application data), and preliminary efficacy (in improving medication adherence and viral suppression) of the PEERNaija app at 6 months. Participants in Arm 1 (PEERNaija) will receive daily medication reminders, peer-based social incentives, and virtual peer social support. Participants in Arm 2 (PEERNaija +) will additionally receive a conditional financial incentive based on their adherence performance. Eligibility for Y-PLWH includes (1) being aged 14–29 years, (2) being on ART, (3) owning a smartphone, (4) being willing to download an app, and (5) being able to read simple text in English.

Discussion

This study will serve as the basis for a larger intervention trial evaluating the PEERNaija app (and the integration of mHealth, incentive, and peer-support-based strategies) to improve HIV outcomes in a critically important region of the world for Y-PLWH.

Trial registration

ClinicalTrials.gov. NCT04930198. First submitted date: May 25, 2021. Study start: August 1, 2021, https://clinicaltrials.gov/. Protocol version: January 21, 2022.