bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in harm reduction service providers professional quality of life during dual public health emergencies in Canada
Authors: Taha Sheena , King Samantha , Atif Sara , Bate Eliza
Published: February 2024

Background

Harm reduction (HR) is a critical response to the pronounced toxicity deaths being experienced in Canada. HR providers report many benefits of their jobs, but also encounter chronic stress from structural inequities and exposure to trauma and death. This research study sought to quantify the emotional toll the toxicity emergency placed on HR providers (Cycle One; 2019). Study objectives were later expanded to determine the impact of the ongoing toxicity as well as the pandemic’s impact on well-being (Cycle Two; 2021).

Methods

Standardized measures of job satisfaction, burnout, secondary traumatic stress, and vulnerability to grief were used in an online national survey. Open-ended questions addressed resources and supports. HR partners across Canada validated the findings and contributed to alternative interpretations and implications.

Results

651 respondents in Cycle One and 1,360 in Cycle Two reported moderately high levels of job satisfaction; they reported finding great meaning in their work. Yet, mean levels of burnout and secondary traumatic stress were moderate, with the latter significantly increasing in Cycle Two. Reported vulnerability to grief was moderate but increased significantly during COVID. When available, supports lacked the quality necessary to respond to the complexities of HR workers’ experiences, or an insufficient number of sessions were covered through benefits. Respondents shared that their professional quality of life was affected more by policy failures and gaps in the healthcare system than it was by the demands of their jobs.

Conclusion

Both the benefits and the strain of providing harm reduction services cannot be underestimated. For HR providers, these impacts are compounded by the drug toxicity emergency, making the service gaps experienced by them all the more critical to address. Implications highlight the need for integration of HR into the healthcare system, sustainable and reliable funding, sufficient counselling supports, and equitable staffing models. Support for this essential workforce is critical to ensuring the well-being of themselves, the individuals they serve, and the health of the broader healthcare system.
Association of preoperative muscle-adipose index measured by computed tomography with survival in patients with esophageal squamous cell carcinoma
Authors: Qian Danqi , Shen Peipei , Zhu Jiahao , Ji Shengjun , Kong Yan
Published: February 2024

Background

Conventional nutritional metrics are closely associated with the prognosis of patients with radically resected esophageal squamous cell carcinoma (ESCC). Nevertheless, the prognostic implications of muscle and adipose tissue composite indexes in ESCC remain unknown.

Methods

We retrospectively analyzed clinicopathological data of 304 patients who underwent resected ESCC. To obtain measurements of the muscle and adipose indexes, preoperative computed tomography (CT) images were used to quantify skeletal-muscle adipose tissue. The diagnostic threshold for muscle-adipose imbalance was determined using X-tile software and used to analyze the association between the muscle-adipose index (MAI) and survival. Instantaneous risk of recurrence was assessed using a hazard function. We constructed a nomogram based on the MAI and other clinical characteristics and established a novel predictive model with independent prognostic factors. The prognostic capabilities of these nomograms were evaluated using calibration curves, receiver operating characteristic (ROC) curves, and decision-curve analysis (DCA).

Results

The overall survival (OS) and disease-free survival (DFS) rates in the muscle-adipose-balanced group were significantly better than those in the muscle-adipose-imbalanced group. Multivariate analyses revealed that the MAI, prognostic nutritional index (PNI), tumor stage, and tumor differentiation were independent prognostic factors for OS and DFS in patients with resected ESCC (P < 0.05). The nuclear density curve indicated a lower risk of recurrence for patients in the muscle-adipose-balanced group than that for their imbalanced counterparts. Conversely, the nuclear density curve for PNI was confounded. Postoperative radiotherapy- (RT) benefit analysis demonstrated that patients with ESCC in the muscle-adipose-balanced group could benefit from adjuvant RT.

Conclusion

This study confirmed that preoperative MAI could serve as a useful independent prognostic factor in patients with resected ESCC. A nomogram based on the MAI and other clinical characteristics could provide individualized survival prediction for patients receiving radical resection. Timely and appropriate nutritional supplements may improve treatment efficacy.
Laparoscopic versus laparotomic surgical treatment in apparent stage I ovarian cancer: a multi-center retrospective cohort study
Authors: Zhang Jing , Li Meiyan , Feng Lan , Zhai Yinjun , Wang Lin , Chen Yuancao
Published: February 2024

Background

Laparoscopic treatment shows non-inferior survival outcomes and better surgical outcomes in apparent stage I ovarian cancer (OC) in some studies but has not been well defined.

Methods

We conducted a retrospective study of patients with apparent stage I OC treated in two hospitals between 2012 and 2022. The surgical and oncologic outcomes were evaluated between patients receiving laparoscopic and laparotomic surgery.

Results

We identified 37 patients with apparent stage I OC, including 15 (40.5%) serous carcinomas, 9 (24.3%) mucinous cancers, 3 (8.1%) endometroid cancers, 2 clear cell carcinomas, and 8 (21.6%) non-epithelial cancers. Sixteen patients received laparoscopic surgery and the other 21 patients underwent laparotomic surgery. The median age (44.5 vs. 49.0 years), mean mass size (10.5 vs. 11.3 cm), and median follow-up time (43.5 vs. 75.0 months) showed no statistically significant differences between patients in laparoscopic and laparotomic groups (all P > 0.05). All the patients underwent comprehensive surgical staging surgery, and the mean surgical time (213.5 vs. 203.3 min, P = 0.507), number of lymph nodes sampling (18.6 vs. 17.5, P = 0.359), proportion of upstaging (12.5% vs. 19.0%, P = 0.680), and postoperative complications (no Accordion Severity Grading System grade ≥ 3) were comparable between two surgical groups. Moreover, patients in the laparoscopic group had significantly less intraoperative blood loss (231.3 vs. 352.4 mL, P = 0.018), shorter interval between surgery and postoperative adjuvant chemotherapy (7.4 vs. 9.5 days, P = 0.004), shorter length of hospital stay (9.9 vs. 13.8 days, P < 0.001) than those treated with laparotomic surgery. During a median follow-up of 54.0 months, 9 (24.3%) relapsed and 1 (2.7%) died, with a 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) rate of 70.6% and 100%, respectively. However, the 5-year RFS (93.3% vs. 58.8%, P = 0.084) and DSS (100% vs. 100%, P = 0.637) rates did not significantly differ between the two groups.

Conclusion

Laparoscopic surgical treatment had less intraoperative blood loss, earlier postoperative adjuvant chemotherapy administration, shorter hospitalization time, and non-inferior survival outcomes in apparent stage I OC when compared with laparotomic surgery.
Impairments of GABAergic transmission in hippocampus mediate increased susceptibility of epilepsy in the early stage of Alzheimer’s disease
Authors: Mao Rui , Hu Mengsha , Liu Xuan , Ye Lei , Xu Bingsong , Sun Min , Xu Siyi , Shao Wenxuan , Tan Yi , Xu Yun , Bai Feng , Shu Shu
Published: February 2024

Background

Patients with Alzheimer’s disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial.

Methods

Four-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated.

Results

APP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV+ Ins) and decreased levels of GABA synthesis and transport. We also found impaired NRG1-ErbB4 signaling which mediated by PV+ Ins loss. And NRG1 administration could effectively reduce seizures and improve cognition in four-month-old APP mice.

Conclusion

Our results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.
From pixels to patient care: deep learning-enabled pathomics signature offers precise outcome predictions for immunotherapy in esophageal squamous cell cancer
Authors: Li Butuo , Qin Wenru , Yang Linlin , Li Haoqian , Jiang Chao , Yao Yueyuan , Cheng Shuping , Zou Bing , Fan Bingjie , Dong Taotao , Wang Linlin
Published: February 2024

Background

Immunotherapy has significantly improved survival of esophageal squamous cell cancer (ESCC) patients, however the clinical benefit was limited to only a small portion of patients. This study aimed to perform a deep learning signature based on H&E-stained pathological specimens to accurately predict the clinical benefit of PD-1 inhibitors in ESCC patients.

Methods

ESCC patients receiving PD-1 inhibitors from Shandong Cancer Hospital were included. WSI images of H&E-stained histological specimens of included patients were collected, and randomly divided into training (70%) and validation (30%) sets. The labels of images were defined by the progression-free survival (PFS) with the interval of 4 months. The pretrained ViT model was used for patch-level model training, and all patches were projected into probabilities after linear classifier. Then the most predictive patches were passed to RNN for final patient-level prediction to construct ESCC-pathomics signature (ESCC-PS). Accuracy rate and survival analysis were performed to evaluate the performance of ViT-RNN survival model in validation cohort.

Results

163 ESCC patients receiving PD-1 inhibitors were included for model training. There were 486,188 patches of 1024*1024 pixels from 324 WSI images of H&E-stained histological specimens after image pre-processing. There were 120 patients with 227 images in training cohort and 43 patients with 97 images in validation cohort, with balanced baseline characteristics between two groups. The ESCC-PS achieved an accuracy of 84.5% in the validation cohort, and could distinguish patients into three risk groups with the median PFS of 2.6, 4.5 and 12.9 months (P < 0.001). The multivariate cox analysis revealed ESCC-PS could act as an independent predictor of survival from PD-1 inhibitors (P < 0.001). A combined signature incorporating ESCC-PS and expression of PD-L1 shows significantly improved accuracy in outcome prediction of PD-1 inhibitors compared to ESCC-PS and PD-L1 anlone, with the area under curve value of 0.904, 0.924, 0.610 for 6-month PFS and C-index of 0.814, 0.806, 0.601, respectively.

Conclusions

The outcome supervised pathomics signature based on deep learning has the potential to enable superior prognostic stratification of ESCC patients receiving PD-1 inhibitors, which convert the images pixels to an effective and labour-saving tool to optimize clinical management of ESCC patients.
Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels
Authors: Wang Jiayi , Chen Pin , Han Guanjie , Zhou Yongjie , Xiang Xingdong , Bian Mengxuan , Huang Lei , Wang Xiang , He Binfeng , Lu Shunyi
Published: February 2024

Background

Peripheral nerve injury (PNI) is commonly observed in clinical practice, yet the underlying mechanisms remain unclear. This study investigated the correlation between the expression of a Ras-related protein Rab32 and pyroptosis in rats following PNI, and potential mechanisms have been explored by which Rab32 may influence Schwann cells pyroptosis and ultimately peripheral nerve regeneration (PNR) through the regulation of Reactive oxygen species (ROS) levels.

Methods

The authors investigated the induction of Schwann cell pyroptosis and the elevated expression of Rab32 in a rat model of PNI. In vitro experiments revealed an upregulation of Rab32 during Schwann cell pyroptosis. Furthermore, the effect of Rab32 on the level of ROS in mitochondria in pyroptosis model has also been studied. Finally, the effects of knocking down the Rab32 gene on PNR were assessed, morphology, sensory and motor functions of sciatic nerves, electrophysiology and immunohistochemical analysis were conducted to assess the therapeutic efficacy.

Results

Silencing Rab32 attenuated PNI-induced Schwann cell pyroptosis and promoted peripheral nerve regeneration. Furthermore, our findings demonstrated that Rab32 induces significant oxidative stress by damaging the mitochondria of Schwann cells in the pyroptosis model in vitro.

Conclusion

Rab32 exacerbated Schwann cell pyroptosis in PNI model, leading to delayed peripheral nerve regeneration. Rab32 can be a potential target for future therapeutic strategy in the treatment of peripheral nerve injuries.
SPOCK2 modulates neuropathic pain by interacting with MT1-MMP to regulate astrocytic MMP-2 activation in rats with chronic constriction injury
Authors: Wang Chenglong , Xu Yitong , Xu Miao , Sun Cong , Zhang Xiaojiao , Tao Xueshu , Song Tao
Published: February 2024

Background

Neuropathic pain (NP) is a kind of intractable pain. The pathogenesis of NP remains a complicated issue for pain management practitioners. SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (SPOCK2) are members of the SPOCK family that play a significant role in the development of the central nervous system. In this study, we investigated the role of SPOCK2 in the development of NP in a rat model of chronic constriction injury (CCI).

Methods

Sprague–Dawley rats were randomly grouped to establish CCI models. We examined the effects of SPOCK2 on pain hpersensitivity and spinal astrocyte activation after CCI-induced NP. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to reflects the pain behavioral degree. Molecular mechanisms involved in SPOCK2-mediated NP in vivo were examined by western blot analysis, immunofluorescence, immunohistochemistry, and co-immunoprecipitation. In addition, we examined the SPOCK2-mediated potential protein–protein interaction (PPI) in vitro coimmunoprecipitation (Co-IP) experiments.

Results

We founded the expression level of SPOCK2 in rat spinal cord was markedly increased after CCI-induced NP, while SPOCK2 downregulation could partially relieve pain caused by CCI. Our research showed that SPOCK2 expressed significantly increase in spinal astrocytes when CCI-induced NP. In addition, SPOCK2 could act as an upstream signaling molecule to regulate the activation of matrix metalloproteinase-2 (MMP-2), thus affecting astrocytic ERK1/2 activation and interleukin (IL)-1β production in the development of NP. Moreover, in vitro coimmunoprecipitation (Co-IP) experiments showed that SPOCK2 could interact with membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14) to regulate MMP-2 activation by the SPARC extracellular (SPARC_EC) domain.

Conclusions

Research shows that SPOCK2 can interact with MT1-MMP to regulate MMP-2 activation, thus affecting astrocytic ERK1/2 activation and IL-1β production to achieve positive promotion of NP.
Ranking the dietary interventions by their effectiveness in the management of polycystic ovary syndrome: a systematic review and network meta-analysis
Authors: Juhász Anna Evelin , Stubnya Márton Péter , Teutsch Brigitta , Gede Noémi , Hegyi Péter , Nyirády Péter , Bánhidy Ferenc , Ács Nándor , Juhász Réka
Published: February 2024

Introduction

Polycystic ovary syndrome (PCOS) is a common condition in women, characterised by reproductive and metabolic dysfunction. While dietary approaches have been evaluated as a first-line treatment for patients with PCOS, there is limited evidence to support preference for a specific dietary composition. This systematic review and network meta-analysis was performed with the objective of comparing different dietary interventions in terms of positive impact. Metformin, the currently preferred treatment, was also compared.

Methods

The latest systematic search was performed on the 20th of March, 2023. Eligible randomised controlled trials (RCTs) included patients with PCOS and compared the dietary approach with another intervention or a standard diet. Outcomes were expressed via anthropometric measurements and hormonal, glycemic, and lipid levels. The Bayesian method was used to perform a network meta-analysis and to calculate the surface under the cumulative ranking curve (SUCRA) values in order to rank the dietary interventions. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system.

Results

19 RCTs were identified, comprising data from 727 patients who were variously treated with 10 types of dietary interventions and metformin. The Dietary Approaches to Stop Hypertension (DASH) diet was the most effective in reducing Homeostatic Model Assessment of Insulin Resistance (SUCRA 92.33%), fasting blood glucose (SUCRA 85.92%), fasting insulin level (SUCRA 79.73%) and triglyceride level (SUCRA 82.07%). For body mass index (BMI), the most effective intervention was the low-calorie diet (SUCRA 84.59%). For weight loss, the low-calorie diet with metformin (SUCRA 74.38%) was the most effective intervention. Metformin produced the greatest reductions in low-density lipoprotein cholesterol (SUCRA 78.08%) and total testosterone levels (SUCRA 71.28%). The low-carb diet was the most effective intervention for reducing cholesterol levels (SUCRA 69.68%), while the normal diet (SUCRA 65.69%) ranked first for increasing high-density lipoprotein cholesterol levels.

Conclusion

Dietary interventions vary in their effects on metabolic parameters in women with PCOS. Based on our results, the DASH diet is the most effective dietary intervention for treating PCOS.

Registration PROSPERO ID CRD42021282984
Gait patterns during overground and virtual omnidirectional treadmill walking
Authors: Lewis Morgan McGrath , Waltz Colin , Scelina Logan , Scelina Kathryn , Owen Kelsey M. , Hastilow Karissa , Zimmerman Eric M. , Rosenfeldt Anson B. , Miller Koop Mandy , Alberts Jay L.
Published: February 2024

Background

Omnidirectional treadmills (ODTs) offer a promising solution to the virtual reality (VR) locomotion problem, which describes the mismatch between visual and somatosensory information and contributes to VR sickness. However, little is known about how walking on ODTs impacts the biomechanics of gait. This project aimed to compare overground and ODT walking and turning in healthy young adults.

Methods

Fifteen young adults completed forward walk, 180° turn, and 360° turn tasks under three conditions: (1) overground, (2) on the Infinadeck ODT in a virtual environment without a handrail, and (3) on the ODT with a handrail. Kinematic data for all walking trials were gathered using 3D optical motion capture.

Results

Overall, gait speed was slower during ODT walking than overground. When controlling for gait speed, ODT walking resulted in shorter steps and greater variability in step length. There were no significant differences in other spatiotemporal metrics between ODT and overground walking. Turning on the ODT required more steps and slower rotational speeds than overground turns. The addition of the stability handrail to the ODT resulted in decreased gait variability relative to the ODT gait without the handrail.

Conclusion

Walking on an ODT resembles natural gait patterns apart from slower gait speed and shorter step length. Slower walking and shorter step length are likely due to the novelty of physically navigating a virtual environment which may result in a more conservative approach to gait. Future work will evaluate how older adults and those with neurological disease respond to ODT walking.
The difference between 2-hour post-challenge and fasting plasma glucose associates with the risk of cardiovascular disease in a normoglycemic population: the Tehran lipid and glucose study
Authors: Abdi Amir , Kohansal Karim , Khalili Davood , Azizi Fereidoun , Hadaegh Farzad
Published: February 2024

Background

Elevated fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2hPG) levels are known to be independent risk factors for cardiovascular disease (CVD). However, there is limited data on the association of the difference between these measures and the risk of CVD. This study aims to investigate this association in normoglycemic Iranian adults, particularly in those with low-normal FPG levels.

Methods

This prospective cohort study included 4,594 30-65-year-old participants from the Tehran Lipid and Glucose Study. Using multivariable Cox proportional hazards regression models adjusting for age, sex, body mass index, hypertension, hypercholesterolemia, smoking, education level and FPG, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the association between 2hPG-FPG, both as continuous and categorical variables, and the CVD risk. Analyses of receiver operating characteristic curves were undertaken to determine the optimal 2hPG-FPG cut-off value.

Results

During a median of 17.9 years of follow-up, 459 CVD events occurred. A one-unit increase in 2hPG-FPG was significantly associated with an elevated risk of cardiovascular disease in both normoglycemic (HR 1.10, 95% CI (1.01–1.19)) and low-normal FPG individuals (HR 1.16, 95% CI (1.04–1.30)); this association resisted adjustment for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among normoglycemic individuals. However, those with 2hPG levels greater than FPG levels had a non-significant increased risk of incident CVD compared to those with 2hPG levels of less than or equal to FPG, with corresponding HR values of 1.18 (95% CI: 0.95–1.46) in normoglycemic and 1.32 (95% CI: 0.98–1.79) in low-normal FPG, respectively. For incident CVD, the optimal cut-off value for the 2hPG-FPG was found to be 1.06 mmol/L, which was applicable for both normoglycemic and low FPG populations; using this criterion, the corresponding risks for incident CVD were 1.36 (95% CI: 1.12–1.64) and 1.57 (95% CI: 1.22–2.03), respectively.

Conclusions

The difference between 2hPG and FPG levels within the normoglycemic range is related to an increased risk of CVD, an issue that was independent of HOMA-IR. A cut-off point for 2hPG-FPG > 1.06 mmol/L may stratify persons at higher risk. These findings were particularly notable in those with low-normal FPG.
A case report of abdominal metastatic dermatofibrosarcoma protuberans misdiagnosed as gastrointestinal stromal tumor
Authors: Deng Minying , Liu Qingxiao , Ren Lei , Yuan Wei , Xu Chen , Hou Yingyong
Published: February 2024

Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant soft-tissue tumor that originates from the skin. It has a slow onset in the early stages, non-specific clinical symptoms, low specificity, and can easily be overlooked, missed, or misdiagnosed by clinicians and pathologists. In addition, DFSP is prone to recurrence after local surgical treatment; however, distant metastasis, especially abdominal metastasis, is rare, which is also a challenge for the accurate diagnosis of DFSP when it progresses distantly. Now a case of abdominal metastasis of DFSP is reported. The patient has been treated with imatinib for ten years, and the lesion has shrunk, but because the patient has been receiving imatinib treatment, his abdominal lesion was once misdiagnosed as gastrointestinal stromal tumor. Therefore, we report on this case to enhance the understanding of the diagnosis and treatment of DFSP, and to provide reference for the pathological diagnosis and precise treatment of such patients.
Structured 3′ UTRs destabilize mRNAs in plants
Authors: Zhang Tianru , Li Changhao , Zhu Jiaying , Li Yanjun , Wang Zhiye , Tong Chun-Yip , Xi Yu , Han Yi , Koiwa Hisashi , Peng Xu , Zhang Xiuren
Published: February 2024

Background

RNA secondary structure (RSS) can influence the regulation of transcription, RNA processing, and protein synthesis, among other processes. 3′ untranslated regions (3′ UTRs) of mRNA also hold the key for many aspects of gene regulation. However, there are often contradictory results regarding the roles of RSS in 3′ UTRs in gene expression in different organisms and/or contexts.

Results

Here, we incidentally observe that the primary substrate of miR159a (pri-miR159a), when embedded in a 3′ UTR, could promote mRNA accumulation. The enhanced expression is attributed to the earlier polyadenylation of the transcript within the hybrid pri-miR159a-3′ UTR and, resultantly, a poorly structured 3′ UTR. RNA decay assays indicate that poorly structured 3′ UTRs could promote mRNA stability, whereas highly structured 3′ UTRs destabilize mRNA in vivo. Genome-wide DMS-MaPseq also reveals the prevailing inverse relationship between 3′ UTRs’ RSS and transcript accumulation in the transcriptomes of Arabidopsis, rice, and even human. Mechanistically, transcripts with highly structured 3′ UTRs are preferentially degraded by 3′–5′ exoribonuclease SOV and 5′–3′ exoribonuclease XRN4, leading to decreased expression in Arabidopsis. Finally, we engineer different structured 3′ UTRs to an endogenous FT gene and alter the FT-regulated flowering time in Arabidopsis.

Conclusions

We conclude that highly structured 3′ UTRs typically cause reduced accumulation of the harbored transcripts in Arabidopsis. This pattern extends to rice and even mammals. Furthermore, our study provides a new strategy of engineering the 3′ UTRs’ RSS to modify plant traits in agricultural production and mRNA stability in biotechnology.
Statistical analysis plan for the phaco TIp position during clear corneal Phacoemulsification Surgery (TIPS) randomized controlled trial
Authors: Kaup Soujanya , Kondal Dimple , Shivalli Siddharudha , Buchan John
Published: February 2024

Background

Cornea is the most important refractive media in the eye, and damage to the corneal endothelium is one of the most common causes of poor visual outcome following cataract surgery, particularly in those with predisposing factors. The role of phaco tip position during phacoemulsification on corneal endothelial damage is ambiguous, and there is no consensus regarding the most cornea-friendly phaco tip position (bevel-up or bevel-down). The objective of the trial is to compare the effect of phaco tip position (bevel-up vs. bevel-down) during phacoemulsification using direct chop technique on corneal endothelial cell count.

Methods and design

TIPS is a randomised, multicentre, parallel-group, triple-masked (participant, outcome assessor, and statistician) trial with 1:1 allocation ratio. A total of 480 eligible participants, aged > 18 years with immature cataract, will be randomly allocated into bevel-up and bevel-down groups at two centres. Randomisation will be stratified according to the cataract grade. The primary outcome is postoperative endothelial cell count at 1 month. Secondary outcomes are central corneal thickness on postoperative days 1, 15, and 30 and difference in intraoperative complications.

Conclusion

In this paper, we describe the detailed statistical analysis plan (SAP) for the TIPS trial, which was prepared prior to database lock. The SAP includes details of planned analyses and unpopulated tables, which will be reported in the publications. We plan to lock the database in July 2023 and publish the results later in the same year.

SAP Version 0.1 (dated: 28 April 2023)

Protocol version:2.0

Trial registration

Clinical Trial Registry of India CTRI/2019/02/017464. Registered on 5 February 2019; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=29764&EncHid=&userName=2019/02/017464
Prediction modeling of cigarette ventilation rate based on genetic algorithm backpropagation (GABP) neural network
Authors: Wei Jiaxin , Wang Zhengwei , Li Shufang , Wang Xiaoming , Xu Huan , Wang Xiushan , Yao Sen , Song Weimin , Wang Youwei , Mei Chao
Published: February 2024

The ventilation rate of cigarettes is an important indicator that affects the internal quality of cigarettes. When producing cigarettes, the unit may experience unstable ventilation rates, which can lead to a decrease in cigarette quality and pose certain risks to smokers. By establishing the ventilation rate prediction model, guide the design of unit parameters in advance, to achieve the goal of stabilizing unit ventilation rate, improve the stability of cigarette ventilation rate, and enhance the quality of cigarettes. This paper used multiple linear regression networks (MLR), backpropagation neural networks (BPNN), and genetic algorithm-optimized backpropagation (GABP) to construct a model for the prediction of cigarette ventilation rate. The model results indicated that the total ventilation rate was significantly positively correlated with weight (P < 0.01), circumference, hardness, filter air permeability, and open resistance. The results showed that the MLR models' (RMSE = 0.652, R2 = 0.841) and the BPNN models’ (RMSE = 0.640, R2 = 0.847) prediction ability were limited. Optimization by genetic algorithm, GABP models were generated and exhibited a little better prediction performance (RMSE = 0.606, R2 = 0.873). The results indicated that the GABP model has the highest accuracy in the prediction of predicting ventilation rate and can accurately predict cigarette ventilation rate. This method can provide theoretical guidance and technical support for the stability study of the ventilation rate of the unit, improve the design and manufacturing capabilities and product quality of short cigarette products, and help to improve the quality of cigarettes.
“For and against” factors influencing participation in personalized breast cancer screening programs: a qualitative systematic review until March 2022
Authors: Laza Celmira , Niño de Guzmán Ena , Gea Montserrat , Plazas Merideidy , Posso Margarita , Rué Montserrat , Castells Xavier , Román Marta
Published: February 2024

Background

Personalized breast cancer screening is a novel strategy that estimates individual risk based on age, breast density, family history of breast cancer, personal history of benign breast lesions, and polygenic risk. Its goal is to propose personalized early detection recommendations for women in the target population based on their individual risk. Our aim was to synthesize the factors that influence women’s decision to participate in personalized breast cancer screening, from the perspective of women and health care professionals.

Methods

Systematic review of qualitative evidence on factors influencing participation in personalized Breast Cancer Screening. We searched in Medline, Web of science, Scopus, EMBASE, CINAHL and PsycINFO for qualitative and mixed methods studies published up to March 2022. Two reviewers conducted study selection and extracted main findings. We applied the best-fit framework synthesis and adopted the Multilevel influences on the cancer care continuum model for analysis. After organizing initial codes into the seven levels of the selected model, we followed thematic analysis and developed descriptive and analytical themes. We assessed the methodological quality with the Critical Appraisal Skills Program tool.

Results

We identified 18 studies published between 2017 and 2022, conducted in developed countries. Nine studies were focused on women (n = 478) and in four studies women had participated in a personalized screening program. Nine studies focused in health care professionals (n = 162) and were conducted in primary care and breast cancer screening program settings. Factors influencing women’s decision to participate relate to the women themselves, the type of program (personalized breast cancer screening) and perspective of health care professionals. Factors that determined women participation included persistent beliefs and insufficient knowledge about breast cancer and personalized screening, variable psychological reactions, and negative attitudes towards breast cancer risk estimates. Other factors against participation were insufficient health care professionals knowledge on genetics related to breast cancer and personalized screening process. The factors that were favourable included the women’s perceived benefits for themselves and the positive impact on health systems.

Conclusion

We identified the main factors influencing women’s decisions to participate in personalized breast cancer screening. Factors related to women, were the most relevant negative factors. A future implementation requires improving health literacy for women and health care professionals, as well as raising awareness of the strategy in society.
[89Zr]Zr-PSMA-617 PET/CT characterization of indeterminate [68Ga]Ga-PSMA-11 PET/CT findings in patients with biochemical recurrence of prostate cancer: lesion-based analysis
Authors: Rosar Florian , Burgard Caroline , Larsen Elena , Khreish Fadi , Marlowe Robert J. , Schaefer-Schuler Andrea , Maus Stephan , Petto Sven , Bartholomä Mark , Ezziddin Samer
Published: February 2024

Background

The state-of-the-art method for imaging men with biochemical recurrence of prostate cancer (BCR) is prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) with tracers containing short-lived radionuclides, e.g., gallium-68 (68Ga; half-life: ∼67.7 min). However, such imaging not infrequently yields indeterminate findings, which remain challenging to characterize. PSMA-targeted tracers labeled with zirconium-89 (89Zr; half-life: ∼78.41 h) permit later scanning, which may help in classifying the level of suspiciousness for prostate cancer of lesions previously indeterminate on conventional PSMA-targeted PET/CT.

Methods

To assess the ability of [89Zr]Zr-PSMA-617 PET/CT to characterize such lesions, we retrospectively analyzed altogether 20 lesions that were indeterminate on prior [68Ga]Ga-PSMA-11 PET/CT, in 15 men with BCR (median prostate-specific antigen: 0.70 ng/mL). The primary endpoint was the lesions’ classifications, and secondary endpoints included [89Zr]Zr-PSMA-617 uptake (maximum standardized uptake value [SUVmax]), and lesion-to-background ratio (tumor-to-liver ratio of the SUVmax [TLR]). [89Zr]Zr-PSMA-617 scans were performed 1 h, 24 h, and 48 h post-injection of 123 ± 19 MBq of radiotracer, 35 ± 35 d post-[68Ga]Ga-PSMA-11 PET/CT.

Results

Altogether, 6/20 previously-indeterminate lesions (30%) were classified as suspicious (positive) for prostate cancer, 14/20 (70%), as non-suspicious (negative). In these two categories, [89Zr]Zr-PSMA-617 uptake and lesional contrast showed distinctly different patterns. In positive lesions, SUVmax and TLR markedly rose from 1 to 48 h, with SUVmax essentially plateauing at high levels, and TLR further steeply increasing, from 24 to 48 h. In negative lesions, uptake, when present, was very low, and decreasing, while contrast was minimal, from 1 to 48 h. No adverse events or clinically-relevant vital signs changes related to [89Zr]Zr-PSMA-617 PET/CT were noted during or ~ 4 weeks after the procedure.

Conclusions

In men with BCR, [89Zr]Zr-PSMA-617 PET/CT may help characterize as suspicious or non-suspicious for prostate cancer lesions that were previously indeterminate on [68Ga]Ga-PSMA-11 PET/CT.

Trial registration

Not applicable.
The volatility mechanism and intelligent fusion forecast of new energy stock prices
Authors: Fan Guo-Feng , Zhang Ruo-Tong , Cao Cen-Cen , Peng Li-Ling , Yeh Yi-Hsuan , Hong Wei-Chiang
Published: February 2024

The new energy industry is strongly supported by the state, and accurate forecasting of stock price can lead to better understanding of its development. However, factors such as cost and ease of use of new energy, as well as economic situation and policy environment, have led to continuous changes in its stock price and increased stock price volatility. By calculating the Lyapunov index and observing the Poincaré surface of the section, we find that the sample of the China Securities Index Green Power 50 Index has chaotic characteristics, and the data indicate strong volatility and uncertainty. This study proposes a new method of stock price index prediction, namely, EWT-S-ALOSVR. Empirical wavelet decomposition extracts features from multiple factors affecting stock prices to form multiple sub-columns with features, significantly reducing the complexity of the stock price series. Support vector regression is well suited for dealing with nonlinear stock price series, and the support vector machine model parameters are selected using random wandering and picking elites via Ant Lion Optimization, making stock price prediction more accurate.
Characteristics of patients with non-cancer pain and long-term prescription opioid use who have used medical versus recreational marijuana
Authors: Davidson Whitney M. , Mahavni Anika , Chrusciel Timothy , Salas Joanne , Miller-Matero Lisa R. , Sullivan Mark D. , Zabel Celeste , Lustman Patrick J. , Ahmedani Brian K. , Scherrer Jeffrey F.
Published: February 2024

Objective

Marijuana use is increasingly common among patients with chronic non-cancer pain (CNCP) and long-term opioid therapy (LTOT). We determined if lifetime recreational and medical marijuana use were associated with more frequent and higher dose prescription opioid use.

Design

Cross-sectional

Subjects

Eligible patients (n=1,037), who had a new period of prescription opioid use lasting 30-90 days, were recruited from two midwestern health care systems to a study of long-term prescription opioid use and mental health outcomes. The present cross-sectional analyses uses baseline data from this on-going cohort study.

Methods

Primary exposures were participant reported lifetime recreational and medical marijuana use versus no lifetime marijuana use. Prescription opioid characteristics included daily versus non-daily opioid use and ≥50 morphine milligram equivalent (MME) dose per day vs. <50 MME. Multivariate, logistic regression models estimated the association between lifetime recreational and medical marijuana use vs. no use and odds of daily and higher dose prescription opioid use, before and after adjusting for confounding.

Results

The sample was an average of 54.9 (SD±11.3) years of age, 57.3% identified as female gender, 75.2% identified as White, and 22.5% identified as Black race. Among all participants, 44.4% were never marijuana users, 21.3% were recreational only, 7.7% medical only and 26.6% were both recreational and medical marijuana users. After controlling for all confounders, lifetime recreational marijuana use, as compared to no use, was significantly associated with increased odds of daily prescription opioid use (OR=1.61; 95%CI:1.02-2.54). There was no association between lifetime recreational or medical marijuana use and daily opioid dose.

Conclusion

Lifetime medical marijuana use is not linked to current opioid dose, but lifetime recreational use is associated with more than a 60% odds of being a daily prescription opioid user. Screening for lifetime recreational marijuana use may identify patients with chronic pain who are vulnerable to daily opioid use which increases risk for adverse opioid outcomes. Prospective data is needed to determine how marijuana use influences the course of LTOT and vice versa.
Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox–Gastaut syndrome and literature review
Authors: Strzelczyk Adam , Becker Hendrik , Tako Lisa , Hock Susanna , Hattingen Elke , Rosenow Felix , Mann Catrin
Published: February 2024

Background

Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE.

Methods

A case of an adult patient with Lennox–Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search.

Results

Four case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases.

Conclusions

Based on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations.

Key points

We summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine.

Refractory SE resolved after 4–7 days on fenfluramine.

Swift fenfluramine up-titration was well-tolerated during SE treatment.

Treatment-emergent adverse events on fenfluramine were not observed.

Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox–Gastaut syndromes.
Successful surgical intervention for acute pyothorax caused by methicillin-resistant Staphylococcus aureus thoracic pyogenic spondylitis: a case report
Authors: Kitamura Naoya , Shimada Yoshifumi , Futakawa Hayato , Makino Hiroto , Takegoshi Yusuke , Kawasuji Hitoshi , Tanabe Keitaro , Ojima Toshihiro , Shimoyama Koichiro , Yamamoto Yoshihiro , Kawaguchi Yoshiharu , Tsuchiya Tomoshi
Published: February 2024

Background

Pyogenic spondylitis or intervertebral discitis rarely spreads into the thoracic cavity, resulting in pyothorax. Moreover, no study has reported methicillin-resistant Staphylococcus aureus (MRSA) as a cause. Conservative and surgical treatments are reportedly effective for the above-mentioned situations; however, there have been no comprehensive reports owing to the disease’s rarity. This report described a case of acute pyothorax due to MRSA-caused pyogenic spondylitis in which surgical intervention with curettage of the intrapleural abscess and simultaneous thoracic vertebral debridement and anterior fixation were effective.

Case presentation

A 60-year-old female with Parkinson’s disease was diagnosed with pyogenic spondylitis caused by MRSA and managed with antibiotics. Subsequently, a right encapsulated pleural effusion was observed, and thoracentesis was performed. No bacteria were identified in the pleural fluid culture; nonetheless, the leukocytes in the fluid increased, and the patient was diagnosed with right acute pyothorax caused by pyogenic spondylitis. Management of the spondylitis and pyothorax before the disease became severe was necessary.

We performed curettage of the intrapleural abscess and vertebral debridement and anterior fixation using an autogenous rib through open thoracotomy. The inflammation or accompanying symptoms did not worsen 3 months after hospital discharge.

Conclusions

Acute pyothorax is rare but may develop from pyogenic spondylitis, for which MRSA is a rarer causative agent. Simultaneous vertebral debridement and anterior fixation, with curettage of the thoracic cavity abscess, may be useful in its management.
Exploring secondary school learners' perceptions of the effectiveness of SOLEs pedagogy in physical sciences as a component of STEM
Authors: Tsamago Hodi , Bayaga Anass
Published: February 2024

The exploratory case study design investigated learners’ perceptions of the effectiveness of self-organized learning environments (SOLEs) pedagogy in physical sciences. Fifteen Grade 11 learners were selected using a purposive sampling method and underwent SOLEs pedagogy instruction for four weeks before they were interviewed through focus group interviews (FGIs). Data were analyzed thematically using the coding method, which was conducted on a sentence-by-sentence basis. The results indicated that learners have a positive perception towards SOLEs pedagogy, because they believe that SOLEs pedagogy enables them to link their classroom experiences with their real-life experiences; it provides them (learners) with an opportunity to simulate practical experiments in the physical sciences; it provides them with multiple channels for receiving information; it enables them to learn collaboratively and limits their reliance on the teacher. Consequently, this study’s findings justify the implementation of SOLEs pedagogy in science education at the secondary school level.