bluuebunny/crossref_metadata_2025_split 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.