bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring substance use disorder discussions in Native American communities: a retrospective Twitter infodemiology study
Authors: Calac Alec J. , McMann Tiana , Cai Mingxiang , Li Jiawei , Cuomo Raphael , Mackey Tim K. 
Published: December 2022

Abstract
Background
The opioid epidemic has had a devastating impact on youth from American Indian and Alaska Native (AI/AN) Tribes and Villages, which also experience disparate suicide rates. The use of publicly available social media data originating from AI/AN communities may enhance public health response time to substance use disorder (SUD)-related overdose and augment Tribal public health surveillance systems, but these concepts have yet to be adequately explored. The goal of this exploratory analysis was to identify primary and secondary accounts of overdose and characterize relevant contextual factors in the AI/AN population on social media.

Methods
The Twitter application programming interface was queried for all Tweets containing geocoded data between March 2014 and June 2020 and filtered for the keyword [‘overdose’]. This sample of Tweets (n = 146,236) was then restricted to those geolocated from US Tribal lands (n = 619). Tweets were manually annotated for primary or secondary accounts of overdose as well as suicidal ideation, substance(s) used, stigma of drug use, and community-wide incidents.

Results
We collected a total of 146,235 tweets that were geocoded and contained the word ‘overdose,’ of which 9.5% were posted on Tribal lands (n = 619). 9.4% of these tweets (n = 58) met our study inclusion criteria and were mainly posted from Oklahoma (n = 26, 45%) and North Carolina (n = 13, 22.4%). Most Tweets (n = 41, 71%) described a primary account of an overdose and were mostly posted from 2014 to 2015. Less than half of the Tweets (n = 27, 46.5%) referenced a specific substance. Those substances mentioned included alcohol, marijuana, methamphetamine, heroin, laundry softener, cocaine, K2-Spice (synthetic cannabinoid), codeine, morphine, Nyquil, and Xanax.

Discussion
Though exploratory, our study identified SUD-related content self-reported by AI/AN communities on Twitter, especially in Oklahoma and North Carolina. These results may assist in the future design and detection of infodemiology trends and early warning signs that can better facilitate intervention specific to the ongoing Tribal opioid epidemic. While all data were collected from the public domain, additional care should be given to individual and community privacy.
Offering a lifestyle intervention to women of premenopausal age as primary prevention for cardiovascular disease? – assessing its cost-effectiveness
Authors: Gao Lan , Moodie Marj 
Published: December 2022

Abstract
Background
There is limited evidence of cost-effective primary prevention interventions for cardiovascular disease (CVD) in young women. This study aimed to assess the value for money of primary prevention of CVD in this population.

Methods
A Markov microsimulation model consisting of both first-ever and recurrent CVD events was developed to simulate the lifetime intervention impact on cost and health outcomes in women of premenopausal age (30 to 54 years) from the Australian healthcare system perspective. The latest wave of the Australian National Health Survey defined the modelled population’s characteristics. The intervention effectiveness of a lifestyle modification program involving changes in diet and physical activity demonstrated to be effective in this population was sourced from a systematic review and meta-analysis. The first-ever and recurrent CVD probabilities were derived from the CVD risk calculators accounting for socio-demographic and clinical characteristics. Costs and utility weights associated with CVD events and long-term management post-CVD were informed by national statistics/published literature. Sensitivity analyses were undertaken to examine the robustness of base case results.

Results
The lifestyle modification program was associated with both higher costs and benefits (in terms of quality-adjusted life years, QALYs) as a primary prevention measure of CVD in premenopausal women, with an ICER of $96,377/QALY or $130,469/LY. The intervention led to fewer first-ever (N = −19) and recurrent CVD events (N = -23) per 10,000 women over the modelled life horizon. The avoided cost due to reduced hospitalisations (−$24) and management (−$164) of CVD could partially offset the cost associated with the intervention ($1560). Sensitivity analysis indicated that time horizon, starting age of the intervention, discount rate, and intervention effectiveness were the key drivers of the results. If the intervention was scaled up to the national level (N = 502,095 at-risk premenopausal women), the total intervention cost would be $794 million with $95 million in healthcare cost-savings.

Conclusion
Offering a lifestyle modification program to premenopausal women in Australia as primary prevention of CVD is not cost-effective from a healthcare system perspective. We should continue to search for new or adapt/optimise existing effective and cost-effective primary prevention measures of CVD for women.
Multi-scale pathology image texture signature is a prognostic factor for resectable lung adenocarcinoma: a multi-center, retrospective study
Authors: Wang Yumeng , Pan Xipeng , Lin Huan , Han Chu , An Yajun , Qiu Bingjiang , Feng Zhengyun , Huang Xiaomei , Xu Zeyan , Shi Zhenwei , Chen Xin , Li Bingbing , Yan Lixu , Lu Cheng , Li Zhenhui , Cui Yanfen , Liu Zaiyi , Liu Zhenbing 
Published: December 2022

Abstract
Background
Tumor histomorphology analysis plays a crucial role in predicting the prognosis of resectable lung adenocarcinoma (LUAD). Computer-extracted image texture features have been previously shown to be correlated with outcome. However, a comprehensive, quantitative, and interpretable predictor remains to be developed.

Methods
In this multi-center study, we included patients with resectable LUAD from four independent cohorts. An automated pipeline was designed for extracting texture features from the tumor region in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) at multiple magnifications. A multi-scale pathology image texture signature (MPIS) was constructed with the discriminative texture features in terms of overall survival (OS) selected by the LASSO method. The prognostic value of MPIS for OS was evaluated through univariable and multivariable analysis in the discovery set (n = 111) and the three external validation sets (V1, n = 115; V2, n = 116; and V3, n = 246). We constructed a Cox proportional hazards model incorporating clinicopathological variables and MPIS to assess whether MPIS could improve prognostic stratification. We also performed histo-genomics analysis to explore the associations between texture features and biological pathways.

Results
A set of eight texture features was selected to construct MPIS. In multivariable analysis, a higher MPIS was associated with significantly worse OS in the discovery set (HR 5.32, 95%CI 1.72–16.44; P = 0.0037) and the three external validation sets (V1: HR 2.63, 95%CI 1.10–6.29, P = 0.0292; V2: HR 2.99, 95%CI 1.34–6.66, P = 0.0075; V3: HR 1.93, 95%CI 1.15–3.23, P = 0.0125). The model that integrated clinicopathological variables and MPIS had better discrimination for OS compared to the clinicopathological variables-based model in the discovery set (C-index, 0.837 vs. 0.798) and the three external validation sets (V1: 0.704 vs. 0.679; V2: 0.728 vs. 0.666; V3: 0.696 vs. 0.669). Furthermore, the identified texture features were associated with biological pathways, such as cytokine activity, structural constituent of cytoskeleton, and extracellular matrix structural constituent.

Conclusions
MPIS was an independent prognostic biomarker that was robust and interpretable. Integration of MPIS with clinicopathological variables improved prognostic stratification in resectable LUAD and might help enhance the quality of individualized postoperative care.
Naturally selected CD7 CAR-T therapy without genetic editing demonstrates significant antitumour efficacy against relapsed and refractory acute myeloid leukaemia (R/R-AML)
Authors: Lu Yu , Liu Ying , Wen Shupeng , Kuang Na , Zhang Xuejun , Li Jianqiang , Wang Fuxu 
Published: December 2022

AbstractBackgroundThe survival rate for patients with relapsed and refractory acute myeloid leukaemia (R/R-AML) remains poor, and treatment is challenging. Chimeric antigen receptor T cells (CAR-T cells) have been widely used for haematologic malignancies. Current CAR-T therapies for acute myeloid leukaemia mostly target myeloid-lineage antigens, such as CD123 and CD33, which may be associated with potential haematopoietic toxicity. As a lineage-specific receptor, CD7 is expressed in acute myeloid leukaemia cells and T cells but is not expressed in myeloid cells. Therefore, the use of CD7 CAR-T cells for R/R-AML needs to be further explored.MethodsIn this report, immunohistochemistry and flow cytometry were used to analyse CD7 expression in clinical samples from R/R-AML patients and healthy donors (HDs). We designed naturally selected CD7 CAR-T cells to analyse various functions and in vitro antileukaemic efficacy based on flow cytometry, and xenograft models were used to validate in vivo tumour dynamics.ResultsWe calculated the percentage of cells with CD7 expression in R/R-AML patients with minimal residual disease (MRD) (5/16, 31.25%) from our institution and assessed CD7 expression in myeloid and lymphoid lineage cells of R/R-AML patients, concluding that CD7 is expressed in T cells but not in myeloid cells. Subsequently, we designed and constructed naturally selected CD7 CAR-T cells (CD7 CAR). We did not perform CD7 antigen knockdown on CD7 CAR-T cells because CD7 molecule expression is naturally eliminated at Day 12 post transduction. We then evaluated the ability to target and kill CD7+acute myeloid leukaemia cells in vitro and in vivo. Naturally selected CD7 CAR-T cells efficiently killed CD7+acute myeloid leukaemia cells and CD7+primary blasts of R/R-AML patients in vitro and significantly inhibited leukaemia cell growth in a xenograft mouse model.ConclusionNaturally selected CD7 CAR-T cells represent an effective treatment strategy for relapsed and refractory acute myeloid leukaemia patients in preclinical studies.
The prebiotic effects of soluble dietary fiber mixture on renal anemia and the gut microbiota in end-stage renal disease patients on maintenance hemodialysis: a prospective, randomized, placebo-controlled study
Authors: Li Yang , Han Min , Song Jia , Liu Shijin , Wang Yongjun , Su Xinhuan , Wei Kai , Xu Zhen , Li Hui , Wang Zunsong 
Published: December 2022

Abstract
Background
Renal anemia is caused by end-stage renal disease (ESRD) but has a complex etiology. The application of dietary fiber (DF) to regulate the gut microbiota has shown effective therapeutic effects in some diseases, but its role in renal anemia is not clear. The aim of this study was to explore the effect of DF on renal anemia by regulating the gut microbiota and its metabolite, short-chain fatty acids (SCFAs).

Methods
A total of 162 ESRD patients were enrolled and randomly distributed into a DF or a control group (received oral DF or potato starch, 10 g/day for 8 weeks). Hemoglobin (Hb), serum iron (Fe2+), serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin and the dosage of recombinant human erythropoietin (rhEPO) before and after intervention in patients were analyzed. The gut microbiota and SCFAs in both groups were analyzed by 16S rDNA sequencing and gas chromatography–mass spectrometry, respectively. Spearman’s correlation test was used to analyze the correlation between the gut microbiota, SCFAs and the hematological indicators.

Results
Compared with the control group, (1) the patients in the DF group had higher Hb [117.0 (12.5) g/L vs. 94.0 (14.5) g/L, p < 0.001], Fe2+ [13.23 (4.83) μmol/L vs. 10.26 (5.55) μmol/L, p < 0.001], and SF levels [54.15 (86.66) ng/ml vs. 41.48 (36.60) ng/ml, p = 0.003]. (2) The rhEPO dosage in the DF group was not significantly decreased (p = 0.12). (3) Bifidobacterium adolescentis, Lactobacillus and Lactobacillaceae were increased in the DF group, and Lactobacillus and Lactobacillaceae were positively correlated with Hb (r = 0.44, p < 0.001; r = 0.44, p < 0.001) and Fe2+ levels (r = 0.26, p = 0.016; r = 0.26, p = 0.016) and negatively correlated with rhEPO dosage (r = − 0.45, p < 0.001; r = − 0.45, p < 0.001). (4) Patients in the DF group had elevated serum butyric acid (BA) levels [0.80 (1.65) vs. 0.05 (0.04), p < 0.001] and BA levels were positively correlated with Hb (r = 0.26, p = 0.019) and Fe2+ (r = 0.31, p = 0.005) and negatively correlated with rhEPO dosage (r = − 0.36, p = 0.001). Lactobacillus and Lactobacillaceae were positively correlated with BA levels (r = 0.78, p < 0.001; r = 0.78, p < 0.001).

Conclusion
DF may improve renal anemia in ESRD patients by regulating the gut microbiota and SCFAs.
Trial registration This study was registered in the China Clinical Trial Registry (www.chictr.org.cn) on December 20, 2018 (ChiCTR1800020232).
Genetic risk factors for ME/CFS identified using combinatorial analysis
Authors: Das Sayoni , Taylor Krystyna , Kozubek James , Sardell Jason , Gardner Steve 
Published: December 2022

AbstractBackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help to alleviate some of these issues for patients.MethodsWe applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case–control design with 1000 cycles of fully random permutation. Results from this study were supported by a series of replication and cohort comparison experiments, including use of disjoint Verbal Interview CFS, post-viral fatigue syndrome and fibromyalgia cohorts also derived from UK Biobank, and compared results for overlap and reproducibility.ResultsCombinatorial analysis revealed 199 SNPs mapping to 14 genes that were significantly associated with 91% of the cases in the ME/CFS population. These SNPs were found to stratify by shared cases into 15 clusters (communities) made up of 84 high-order combinations of between 3 and 5 SNPs.p-values for these communities range from 2.3 × 10–10to 1.6 × 10–72. Many of the genes identified are linked to the key cellular mechanisms hypothesized to underpin ME/CFS, including vulnerabilities to stress and/or infection, mitochondrial dysfunction, sleep disturbance and autoimmune development. We identified 3 of the critical SNPs replicated in the post-viral fatigue syndrome cohort and 2 SNPs replicated in the fibromyalgia cohort. We also noted similarities with genes associated with multiple sclerosis and long COVID, which share some symptoms and potentially a viral infection trigger with ME/CFS.ConclusionsThis study provides the first detailed genetic insights into the pathophysiological mechanisms underpinning ME/CFS and offers new approaches for better diagnosis and treatment of patients.
Sirtuin 5 aggravates microglia-induced neuroinflammation following ischaemic stroke by modulating the desuccinylation of Annexin-A1
Authors: Xia Qian , Gao Shuai , Han Tangrui , Mao Meng , Zhan Gaofeng , Wang Yonghong , Li Xing 
Published: December 2022

Abstract
Background
Microglia-induced excessive neuroinflammation plays a crucial role in the pathophysiology of multiple neurological diseases, such as ischaemic stroke. Controlling inflammatory responses is considered a promising therapeutic approach. Sirtuin 5 (SIRT5) mediates lysine desuccinylation, which is involved in various critical biological processes, but its role in ischaemic stroke remains poorly understood. This research systematically explored the function and potential mechanism of SIRT5 in microglia-induced neuroinflammation in ischaemic stroke.

Methods
Mice subjected to middle cerebral artery occlusion were established as the animal model, and primary cultured microglia treated with oxygen–glucose deprivation and reperfusion were established as the cell model of ischaemic stroke. SIRT5 short hairpin RNA, adenovirus and adeno-associated virus techniques were employed to modulate SIRT5 expression in microglia both in vitro and in vivo. Coimmunoprecipitation, western blot and quantitative real-time PCR assays were performed to reveal the molecular mechanism.

Results
In the current study, we showed that SIRT5 expression in microglia was increased in the early phase of ischaemic stroke. SIRT5 interacts with and desuccinylates Annexin A1 (ANXA1) at K166, which in turn decreases its SUMOylation level. Notably, the desuccinylation of ANXA1 blocks its membrane recruitment and extracellular secretion, resulting in the hyperactivation of microglia and excessive expression of proinflammatory cytokines and chemokines, ultimately leading to neuronal cell damage after ischaemic stroke. Further investigation showed that microglia-specific forced overexpression of SIRT5 worsened ischaemic brain injury, whereas downregulation of SIRT5 exhibited neuroprotective and cognitive-preserving effects against ischaemic brain injury, as proven by the decreased infarct area, reduced neurological deficit scores, and improved cognitive function.

Conclusions
Collectively, these data identify SIRT5 as a novel regulator of microglia-induced neuroinflammation and neuronal damage after cerebral ischaemia. Interventions targeting SIRT5 expression may represent a potential therapeutic target for ischaemic stroke.
Human-prosthesis cooperation: combining adaptive prosthesis control with visual feedback guided gait
Authors: Fylstra Bretta L. , Lee I-Chieh , Li Minhan , Lewek Michael D. , Huang He 
Published: December 2022

Abstract
Background
Personalizing prosthesis control is often structured as human-in-the-loop optimization. However, gait performance is influenced by both human control and intelligent prosthesis control. Hence, we need to consider both human and prosthesis control, and their cooperation, to achieve desired gait patterns. In this study, we developed a novel paradigm that engages human gait control via user-fed visual feedback (FB) of stance time to cooperate with automatic prosthesis control tuning. Three initial questions were studied: (1) does user control of gait timing (via visual FB) help the prosthesis tuning algorithm to converge faster? (2) in turn, does the prosthesis control influence the user’s ability to reach and maintain the target stance time defined by the feedback? and (3) does the prosthesis control parameters tuned with extended stance time on prosthesis side allow the user to maintain this potentially beneficial behavior even after feedback is removed (short- and long-term retention)?

Methods
A reinforcement learning algorithm was used to achieve prosthesis control to meet normative knee kinematics in walking. A visual FB system cued the user to control prosthesis-side stance time to facilitate the prosthesis tuning goal. Seven individuals without amputation (AB) and four individuals with transfemoral amputation (TFA) walked with a powered knee prosthesis on a treadmill. Participants completed prosthesis auto-tuning with three visual feedback conditions: no FB, self-selected stance time FB (SS FB), and increased stance time FB (Inc FB). The retention of FB effects was studied by comparing the gait performance across three different prosthesis controls, tuned with different visual FB.

Results
(1) Human control of gait timing reduced the tuning duration in individuals without amputation, but not for individuals with TFA. (2) The change of prosthesis control did not influence users’ ability to reach and maintain the visual FB goal. (3) All participants increased their prosthesis-side stance time with the feedback and maintain it right after feedback was removed. However, in the post-test, the prosthesis control parameters tuned with visual FB only supported a few participants with longer stance time and better stance time symmetry.

Conclusions
The study provides novel insights on human-prosthesis interaction when cooperating in walking, which may guide the future successful adoption of this paradigm in prosthesis control personalization or human-in-the-loop optimization to improve the prosthesis user’s gait performance.
Sequential interventions to maintain the safety and service provisions of human milk banking in India: keeping up with the call to action in response to the COVID-19 pandemic
Authors: Bhasin Maheshwar , Nangia Sushma , Kumar Gunjana , Parihar Abha , Goel Srishti 
Published: December 2022

Abstract
Background
WHO recommends donor milk as the next best choice if Mothers’ own milk (MOM) is unavailable. At our milk bank, during the COVID 19 pandemic, we observed a steep decline in the collection of donor milk, while Pasteurised Donor human milk (PDHM) demand increased. This called for active intervention.

Methods
We employed the quasi-experimental quality improvement initiative. During September 2020 (baseline period) the team members identified modifiable bottlenecks and suggested interventions (using WhatsApp to increase follow up, telehealth and digital tools) which were implemented in October 2020 and the impact was evaluated till March 2021. The SMART aim was “to meet the demand (estimated as 15,000 ml/month) of donor milk for adjoining 80-bedded NICU”. Process measures were; daily amount of donor milk collected, pasteurized donor milk disbursed to NICU, number of donors and frequency of donations. The balancing measure was that the collection of donor milk should not undermine the provision of freshly expressed MOM for babies.

Results
Collection of donor milk increased by 180% from baseline during the Intervention phase. This was sustained throughout the sustenance phase (November 2020 and March 2021) with an average monthly collection of 16,500 ml. Strikingly, the increased follow-up of mothers with emphasis on MOM decreased the NICU’s donor milk requirement from 13,300 ml (baseline) to 12,500 ml (intervention) to 8,300 ml (sustenance). Monitoring of daily MOM used in the NICU revealed a 32% surge from 20,000 ml (baseline) to 27,000 ml (intervention) sustained at 25,000 ml per month.

Conclusion
By improving the provisions of human milk banks, near-exclusive human milk feeding can be ensured even during the pandemic time.