bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of advertised versus actual cannabidiol (CBD) content of oils, aqueous tinctures, e-liquids and drinks purchased in the UK
Authors: Johnson Drusus A. , Hogan Megan , Marriot Ray , Heaney Liam M. , Bailey Stephen J. , Clifford Tom , James Lewis J. 
Published: July 2023

Abstract
Background
Cannabidiol (CBD)-containing products are sold widely in consumer stores, but concerns have been raised regarding their quality, with notable discrepancies between advertised and actual CBD content. Information is limited regarding how different types of CBD products may differ in their deviation from advertised CBD concentrations. Therefore, CBD concentrations were quantified and compared in aqueous tinctures, oils, e-liquids and drinks.

Methods
Products (13 aqueous tinctures, 29 oils, 10 e-liquids and 11 drinks) were purchased online in the UK. CBD concentrations were quantified in aqueous tinctures, oils and e-liquids via high performance liquid chromatography (HPLC), and in drinks via gas chromatograhy-mass spectrometry (GC-MS).

Results
Measured concentrations fell −25.7 ± 17.3, −6.1 ± 7.8, −6.9 ± 4.6 and − 0.03 ± 0.06 mg/mL below advertised concentrations for aqueous tinctures, oils, e-liquids and drinks, respectively (medians ± interquartile ranges; p < .05). Oils deviated relatively less (−19.0 ± 14.5%) from advertised concentrations than e-liquids (−29.2 ± 10.2%), aqueous tinctures (−51.4 ± 41.4%) and drinks (−65.6 ± 36.5%; p < .01), whilst e-liquids deviated less than aqueous tinctures and drinks (p < .05), and deviation was not different between aqueous tinctures and drinks (p = .19). Only 5/63 (8%) products had measured concentrations within 10% of advertised concentrations.

Discussion
Similarly to previous studies, few products had measured CBD concentrations within 10% of advertised concentrations, with most falling below advertised concentrations. All individual product types deviated from advertised concentrations, with oils deviating least. These findings may be indicative of poor manufacturing standards, or that CBD undergoes degradation in consumer products. This reinforces concerns over quality of CBD-containing consumer products and may highlight the need for improved regulation of such products.
Fire regimes over a 1070-m elevational gradient, San Francisco Peaks/Dook’o’oosłííd, Arizona, USA
Authors: Fulé Peter Z. , Barrett Molly Peige , Cocke Allison E. , Crouse Joseph E. , Roccaforte John P. , Normandin Donald P. , Covington W. Wallace , Moore Margaret M. , Heinlein Thomas A. , Stoddard Michael T. , Rodman Kyle C. 
Published: July 2023

Abstract
Background
Steep elevational gradients bring multiple forest types and fire regimes together in close proximity. The San Francisco Peaks/Dook’o’oosłííd in northern Arizona rise to 3851 m elevation with slopes that span many of the major forest types of the southwestern US mountains. To reconstruct past fire regimes across this broad elevational gradient, we sampled fire-scarred trees across the south face of the Peaks, complementing previous research on forest structure, composition, and origin of aspen stands.

Results
At the highest elevations, Rocky Mountain bristlecone pine forests had a mean fire interval (MFI) of 19.7 years prior to a modern fire exclusion period beginning after 1879. Other high-elevation (> 2800 m) mixed conifer forests had MFI = 5.7 years and low-elevation (< 2,800 m) pine forests had MFI = 4.0 years. After 1879, there were no large fires through the end of the twentieth century. Before 1879, fires occurred in the early to middle growing season, and fire event years were linked to climate across all elevations, with a stronger association to drought (i.e., the Palmer Drought Severity Index) than to El Niño-Southern Oscillation phase. Pulses of forest regeneration were associated with the fire regime, with the largest pulse occurring shortly after fire exclusion. In addition to fire exclusion, other factors such as post-fire sprouting and regeneration after tree harvesting likely contributed to the current dense forest structure on the Peaks.

Conclusions
Following over a century of fire exclusion, fire activity has increased on the Peaks over the past two decades, with large recent fires of uncharacteristic severity raising concerns about tree mortality, erosion, flooding, and infrastructure damage in surrounding human communities. Past fire regimes provide useful insight into fire-climate-forest interactions and the conditions under which existing forest communities were well adapted, but adaption to future conditions is likely to be challenging due to the rapid pace of projected environmental changes.
Prevalence and economic burden of dementia in the Arab world
Authors: Qassem Tarik , Itani Lynn , Nasr Walid , Al-Ayyat Dania , Javaid Syed Fahad , Al-Sinawi Hamed 
Published: July 2023

Background
The growing prevalence of dementia is a global concern, especially in the Arab world, where updated economic impact data are scarce. Understanding its prevalence and cost is crucial for effective policies and support systems.

Aims
To estimate dementia prevalence and cost in Arab countries for 2021.

Method
United Nations population data and dementia prevalence estimates were used to calculate total cases. Direct costs were based on gross domestic product (GDP) per capita (purchasing power parity) and income classification. Indirect caregiver support costs were estimated using average monthly wages and two distinct scenarios.

Results
The highest dementia prevalence among those aged more than 60 years was in Lebanon (4.88%), Tunisia (4.43%) and Algeria (4.19%). The total direct cost in the Arab region was $8.18 billion for those over 50 years old. Indirect costs ranged from $2.25 billion (best case) to $5.67 billion (worst case), with a mean value of $3.98 billion. Total dementia care costs (direct and indirect) under the mean scenario for the entire Arab world amounted to $12.17 billion, with costs as a percentage of GDP ranging from 0.05% (Sudan) to 0.44% (Lebanon).

Conclusions
This study highlights dementia as a growing public health issue in the Arab world, with 1 329 729 individuals affected in 2021 and total costs between $10.43 billion and $13.90 billion. The findings emphasise the urgent need for investment in research and specialised services for older adults, particularly those with dementia.
Elevated Preoperative TPO Ab Titers Decrease Risk for DTC in a Linear Fashion: A Retrospective Analysis of 1635 Cases
Authors: Paparodis Rodis , Livadas Sarantis , Karvounis Evangelos , Bantouna Dimitra , Zoupas Ioannis , Angelopoulos Nicholaos , Imam Shahnawaz , Jaume Juan Carlos 
Published: July 2023

Abstract

Context
For some, chronic lymphocytic thyroiditis (Hashimoto thyroiditis) is an important risk factor for differentiated thyroid cancer (DTC). Surgical cohort studies even suggested a potential role for thyroid peroxidase antibodies (TPO-Abs) on that risk.

Objective
Our clinical observations argued against that possibility. We designed the present study to evaluate the relationship of TPO-Abs and DTC in a large patient population.

Methods
We recruited individuals who underwent thyroidectomies at 4 different clinical sites (USA: 1 clinic, 2000-2013, and Greece: 3 clinics, 2007-2021). We gathered data on TPO-Abs titers measured with commercially available chemiluminescence immunoassays, and reviewed patients’ data including surgical pathology. TPO-Abs of 34 IU/mL or greater was deemed positive (TPO+) and TPO-Abs less than 34 IU/mL was deemed negative (TPO–). Odds ratios (OR) for DTC were calculated with the Fisher exact test and P less than .05 was deemed significant.

Results
We reviewed data from 8461 consecutive thyroid surgery cases. TPO-Abs titers were available for 1635 individuals: DTC n = 716 (43.8%), benign pathology n = 919 (56.2%), TPO+ n = 540 (33.0%), and TPO− n = 1095 (67.0%). DTC was found at a lower frequency in TPO+ (198/540, 36.7%) compared to TPO− (518/1095, 47.3%) patients, OR 0.64 (0.52-0.80; P &lt; .0001). Rising TPO-Abs titers conferred protection against DTC in a linear fashion: TPO-Abs less than 10 IU/mL: 59.3%, TPO-Abs less than 34 IU/mL: 47.4%, TPO-Abs 34 to 100 IU/mL: 42.6%, TPO-Abs 100 to 500 IU/mL: 32.0%, TPO-Abs greater than 1000 IU/mL: 19.4%; P less than .0001.

Conclusion
Higher TPO-Ab titers appear protective against DTC in our large multicenter cohort of patients who underwent thyroidectomies. Rising preoperative TPO-Abs titers conferred linearly increasing protection against DTC.
Growth Hormone Treatment for Non-GHD Disorders: Excitement Tempered by Biology
Authors: Grimberg Adda , Hawkes Colin P 
Published: July 2023

Abstract
The success of growth hormone (GH) replacement in children with classical GH deficiency has led to excitement that other causes of short stature may benefit similarly. However, clinical experience has shown less consistent and generally less dramatic effects on adult height, perhaps not surprising in light of increased understanding of GH and growth plate biology. Nonetheless, clinical demand for GH treatment continues to grow. Upon the 20th anniversary of the US Food and Drug Administration's approval of GH treatment for idiopathic short stature, this review will consider the factors underlying the expansion of GH treatment, the biological mechanisms of GH action, the non-GH–deficient uses of GH as a height-promoting agent, biological constraints to GH action, and future directions.
Mapping Pregnancy-dependent Sulfhydrome Unfolds Diverse Functions of Protein Sulfhydration in Human Uterine Artery
Authors: Bai Jin , Jiao Fenglong , Salmeron Alejandra Garcia , Xu Shi , Xian Ming , Huang Lan , Chen Dong-bao 
Published: July 2023

Abstract
Uterine artery (UA) hydrogen sulfide (H2S) production is augmented in pregnancy and, on stimulation by systemic/local vasodilators, contributes to pregnancy-dependent uterine vasodilation; however, how H2S exploits this role is largely unknown. S-sulfhydration converts free thiols to persulfides at reactive cysteine(s) on targeted proteins to affect the entire proteome posttranslationally, representing the main route for H2S to elicit its function. Here, we used Tag-Switch to quantify changes in sulfhydrated (SSH-) proteins (ie, sulfhydrome) in H2S-treated nonpregnant and pregnant human UA. We further used the low-pH quantitative thiol reactivity profiling platform by which paired sulfhydromes were subjected to liquid chromatography tandem mass spectrometry–based peptide sequencing to generate site (cysteine)-specific pregnancy-dependent H2S-responsive human UA sulfhydrome. Total levels of sulfhydrated proteins were significantly greater in pregnant vs nonpregnant human UA and further stimulated by treatment with sodium hydrosulfide. We identified a total of 360 and 1671 SSH-peptides from 480 and 1186 SSH-proteins in untreated and sodium hydrosulfide–treated human UA, respectively. Bioinformatics analyses identified pregnancy-dependent H2S-responsive human UA SSH peptides/proteins, which were categorized to various molecular functions, pathways, and biological processes, especially vascular smooth muscle contraction/relaxation. Pregnancy-dependent changes in these proteins were rectified by immunoblotting of the Tag-Switch labeled SSH proteins. Low-pH quantitative thiol reactivity profiling failed to identify low abundance SSH proteins such as KATP channels in human UA; however, immunoblotting of Tag-Switch–labeled SSH proteins identified pregnancy-dependent upregulation of SSH-KATP channels without altering their total proteins. Thus, comprehensive analyses of human UA sulfhydromes influenced by endogenous and exogenous H2S inform novel roles of protein sulfhydration in uterine hemodynamics regulation.
Vasopressin Expressed in Hypothalamic CRF Neurons Causes Impaired Water Diuresis in Secondary Adrenal Insufficiency
Authors: Yamagata Satoshi , Talukder Ashraf H , Murasawa Shingo , Niioka Kanako , Kumagai Naoya , Takagi Mao , Kawamura Meiko , Natsume Rie , Abe Manabu , Uchida Katsuya , Sato Tatsuya , Kurose Akira , Kageyama Kazunori , Daimon Makoto , Sakimura Kenji , Itoi Keiichi 
Published: July 2023

Abstract
Patients with secondary adrenal insufficiency can present with impaired free water excretion and hyponatremia, which is due to the enhanced secretion of vasopressin (AVP) despite increased total body water. AVP is produced in magnocellular neurons in the paraventricular nucleus of the hypothalamus (PVH) and supraoptic nucleus and in parvocellular corticotropin-releasing factor (CRF) neurons in the PVH. This study aimed to elucidate whether magnocellular AVP neurons or parvocellular CRF neurons coexpressing AVP are responsible for the pathogenesis of hyponatremia in secondary adrenal insufficiency. The number of CRF neurons expressing copeptin, an AVP gene product, was significantly higher in adrenalectomized AVP-floxed mice (AVPfl/fl) than in sham-operated controls. Adrenalectomized AVPfl/fl mice supplemented with aldosterone showed impaired water diuresis under ad libitum access to water or after acute water loading. They became hyponatremic after acute water loading, and it was revealed under such conditions that aquaporin-2 (AQP2) protein levels were increased in the kidney. Furthermore, translocation of AQP2 to the apical membrane was markedly enhanced in renal collecting duct epithelial cells. Remarkably, all these abnormalities observed in the mouse model for secondary adrenal insufficiency were ameliorated in CRF-AVP−/− mice that lacked AVP in CRF neurons. Our study demonstrates that CRF neurons in the PVH are responsible for the pathogenesis of impaired water excretion in secondary adrenal insufficiency.
Spinal Navigation for Lateral Instrumentation of the Thoracolumbar Spine
Authors: Schwendner Maximilian , Liang Raimunde , Butenschöen Vicki M. , Krieg Sandro M. , Ille Sebastian , Meyer Bernhard 
Published: July 2023

BACKGROUND AND OBJECTIVES:
Three-dimensional imaging-based navigation in spine surgery is mostly applied for pedicle screw placement. However, its potential reaches beyond. In this study, we analyzed the incorporation of spinal navigation for lateral instrumentation of the thoracolumbar spine in clinical routine at a high-volume spine center.

METHODS:
Patients scheduled for lateral instrumentation were prospectively enrolled. A reference array was attached to the pelvis, and a computed tomography scan was acquired intraoperatively. A control computed tomography scan was routinely performed after final cage placement, replacing conventional 2-dimensional X-ray imaging.

RESULTS:
145 cases were enrolled from April to October 2021 with a median of 1 (1-4) level being instrumented. Indications for surgery were trauma (35.9%), spinal infection (31.7%), primary and secondary tumors of the spine (17.2%), and degenerative spine disease (15.2%). The duration of surgery after the first scan was 98 ± 41 (20-342) minutes. In total, 190 cages were implanted (94 expandable cages for vertebral body replacement (49.5%) and 96 cages for interbody fusion [50.5%]). Navigation was successfully performed in 139 cases (95.9%). The intraoperative mental load was rated on a scale from 0 to 150 (maximal effort) by the surgeons, showing a moderate effort (median 30 [10-120]).

CONCLUSION:
Three-dimensional imaging-based spinal navigation can easily be incorporated in clinical routine and serves as a reliable tool to achieve precise implant placement in lateral instrumentation of the spine. It helps to minimize radiation exposure to the surgical staff.
Performance in a Simulated Virtual Reality Anterior Cervical Discectomy and Fusion Task: Disc Residual, Rate of Removal, and Efficiency Analyses
Authors: Bakhaidar Mohamad , Alsayegh Ahmad , Yilmaz Recai , Fazlollahi Ali M. , Ledwos Nicole , Mirchi Nykan , Winkler-Schwartz Alexander , Luo Lucy , Del Maestro Rolando F. 
Published: July 2023

BACKGROUND AND OBJECTIVES:
Anterior cervical discectomy and fusion (ACDF) is among the most common spine procedures. The Sim-Ortho virtual reality simulator platform contains a validated ACDF simulated task for performance assessment. This study aims to develop a methodology to extract three-dimensional data and reconstruct and quantitate specific simulated disc tissues to generate novel metrics to analyze performance metrics of skilled and less skilled participants.

METHODS:
We used open-source platforms to develop a methodology to extract three-dimensional information from ACDF simulation data. Metrics generated included, efficiency index, disc volumes removed from defined regions, and rate of tissue removal from superficial, central, and deep disc regions. A pilot study was performed to assess the utility of this methodology to assess expertise during the ACDF simulated procedure.

RESULTS:
The system outlined, extracts data allowing the development of a methodology which accurately reconstructs and quantitates 3-dimensional disc volumes. In the pilot study, data sets from 27 participants, divided into postresident, resident, and medical student groups, allowed assessment of multiple novel metrics, including efficiency index (surgical time spent in actively removing disc), where the postresident group spent 61.8% of their time compared with 53% and 30.2% for the resident and medical student groups, respectively (P = .01). During the annulotomy component, the postresident group removed 47.4% more disc than the resident groups and 102% more than the medical student groups (P = .03).

CONCLUSION:
The methodology developed in this study generates novel surgical procedural metrics from 3-dimensional data generated by virtual reality simulators and can be used to assess surgical performance.
A TGF-β-responsive enhancer regulates SRC expression and epithelial–mesenchymal transition-associated cell migration
Authors: Noshita Soshi , Kubo Yuki , Kajiwara Kentaro , Okuzaki Daisuke , Nada Shigeyuki , Okada Masato 
Published: July 2023

ABSTRACT
The non-receptor tyrosine kinase SRC is overexpressed and/or hyperactivated in various human cancers, and facilitates cancer progression by promoting invasion and metastasis. However, the mechanisms underlying SRC upregulation are poorly understood. In this study, we demonstrate that transforming growth factor-β (TGF-β) induces SRC expression at the transcriptional level by activating an intragenic the SRC enhancer. In the human breast epithelial cell line MCF10A, TGF-β1 stimulation upregulated one of the SRC promotors, the 1A promoter, resulting in increased SRC mRNA and protein levels. Chromatin immunoprecipitation (ChIP)-sequencing analysis revealed that the SMAD complex is recruited to three enhancer regions ∼15 kb upstream and downstream of the SRC promoter, and one of them is capable of activating the SRC promoter in response to TGF-β. JUN, a member of the activator protein (AP)-1 family, localises to the enhancer and regulates TGF-β-induced SRC expression. Furthermore, TGF-β-induced SRC upregulation plays a crucial role in epithelial–mesenchymal transition (EMT)-associated cell migration by activating the SRC–focal adhesion kinase (FAK) circuit. Overall, these results suggest that TGF-β-induced SRC upregulation promotes cancer cell invasion and metastasis in a subset of human malignancies.
Selective breeding for high voluntary exercise in mice increases maximal (V̇O2,max) but not basal metabolic rate
Authors: Schwartz Nicole E. , McNamara Monica P. , Orozco Jocelyn M. , Rashid Jaanam O. , Thai Angie P. , Garland Theodore 
Published: July 2023

ABSTRACT
In general, sustained high rates of physical activity require a high maximal aerobic capacity (V̇O2,max), which may also necessitate a high basal aerobic metabolism (BMR), given that the two metabolic states are linked via shared organ systems, cellular properties and metabolic pathways. We tested the hypotheses that (a) selective breeding for high voluntary exercise in mice would elevate both V̇O2,max and BMR, and (b) these increases are accompanied by increases in the size of some internal organs (ventricle, triceps surae muscle, liver, kidney, spleen, lung, brain). We measured 72 females from generations 88 and 96 of an ongoing artificial selection experiment comprising four replicate High Runner (HR) lines bred for voluntary daily wheel-running distance and four non-selected control lines. With body mass as a covariate, HR lines as a group had significantly higher V̇O2,max (+13.6%, P&lt;0.0001), consistent with previous studies, but BMR did not significantly differ between HR and control lines (+6.5%, P=0.181). Additionally, HR mice did not statistically differ from control mice for whole-body lean or fat mass, or for the mass of any organ collected (with body mass as a covariate). Finally, mass-independent V̇O2,max and BMR were uncorrelated (r=0.073, P=0.552) and the only statistically significant correlation with an organ mass was for V̇O2,max and ventricle mass (r=0.285, P=0.015). Overall, our results indicate that selection for a behavioral trait can yield large changes in behavior without proportional modifications to underlying morphological or physiological traits.
Impact of Indocyanine Green Fluorescence Imaging on Lymphadenectomy Quality During Laparoscopic Distal Gastrectomy for Gastric Cancer (Greeneye): An Adaptative, Phase 2, Clinical Trial
Authors: Sposito Carlo , Maspero Marianna , Conalbi Valeria , Magarotto Andrea , Altomare Michele , Battiston Carlo , Cantù Paolo , Mazzaferro Vincenzo 
Published: July 2023

Abstract
Background
Indocyanine green (ICG)-guided lymphadenectomy using near-infrared visualization (NIR) may increase nodal yield during gastrectomy. The purpose of this study was to evaluate the clinical benefit of NIR visualization on the quality of D2 lymphadenectomy during laparoscopic distal gastrectomy.

Methods
This single-arm, open-label, Simon’s two-stage, adaptive, phase 2 trial included patients who underwent laparoscopic distal gastrectomy for gastric adenocarcinoma. Endoscopic peritumoral injection of ICG was performed 24 ± 6 h before surgery. Intraoperatively, after standard D2 lymphadenectomy and specimen extraction, NIR was used for eventual completion lymphadenectomy. The primary endpoint was clinical benefit of NIR (i.e., at least one additional harvested station containing lymph nodes, with negative points for every harvested station with no lymph nodes at final pathology).

Results
We enrolled 18 patients (61% female, median age 69 years). With NIR, an extra 23 stations were harvested: 9 contained no lymph nodes, 12 contained nonmetastatic lymph nodes, and 2 contained metastatic lymph nodes. The most commonly visualized station with NIR were station 6 (8 patients) and 1 (4 patients). The total number of harvested nodes per patient was 32 (interquartile range [IQR] 26–41), with a median of 1 (IQR 0–1) additional lymph node after NIR. Overall, seven (39%) patients had a clinical benefit from NIR, of which two (11%) had one metastatic lymph node harvested with NIR.

Conclusions
NIR visualization improves the quality of D2 lymphadenectomy in distal gastrectomy for gastric cancer. Considering the limited improve in the number of harvested lymph nodes, its real oncological benefit is still questionable.