bluuebunny/crossref_metadata_2025_split huggingface dataset:
Best practice guide for patellofemoral pain based on synthesis of a systematic review, the patient voice and expert clinical reasoning
Authors: Neal Bradley Stephen , Lack Simon David , Bartholomew Clare , Morrissey Dylan 
Published: October 2024

ObjectiveDefine a best practice guide for managing people with patellofemoral pain (PFP).MethodsA mixed-methods convergent segregated synthesis of meta-analysed data with a thematic analysis of semistructured interviews and focus groups. Agreement between subproject results informed the strength of clinical recommendation for interventions eligible for best practice recommendation.Data sourcesMedline, Web of Science, Scopus, reference lists and citation tracking; semistructured interviews of people with PFP; and semistructured interviews and focus groups with clinical experts.Eligibility criteriaHigh-quality (PEDro scale >7) randomised controlled trials (RCTs) were retained for efficacy estimation using meta-analysis. People with PFP were required to have experienced an episode of care in the past 6 months and clinical experts were required to have>5 years of clinical experience alongside direct involvement in research.ResultsData from 65 high-quality RCTs involving 3796 participants informed 11 meta-analyses of interventions. Interviews with 12 people with PFP led to 3 themes and interviews with 19 clinical experts led to 4 themes. These were further explored in three clinical expert focus groups. Best practice for PFP should first involve understanding a patient’s background risk factors, their reasons for seeking care, greatest symptoms, and physical impairments, to inform treatment selection. Synthesis led to six distinct interventions being recommended. Knee-targeted±hip-targeted exercise therapy underpinned by education should be delivered, with additional supporting interventions such as prefabricated foot orthoses, manual therapy, movement/running retraining, or taping decided on and tailored to a patient’s needs and preferences.ConclusionA best practice guide based on a synthesis of three data streams recommends that exercise therapy and education be delivered as the primary intervention for people with PFP. Prescription of other supporting interventions should be aligned with the individual patient’s particular presentation following a thorough assessment.
Global landscape of nicotine and tobacco products additives policies
Authors: Oliveira da Silva Andre Luiz , Bialous Stella 
Published: October 2024

IntroductionProduct design is a key tobacco industry strategy to recruit consumers and hinder cessation. An important technology in tobacco product design is the use of additives including those that create characterising flavours, that is, flavours that are perceived by taste and or smell by the user. To curb youth use, many countries are implementing policies to limit the use of flavours and other additives in tobacco products. This paper reviews the global landscape of tobacco additives policies including those focusing only on flavouring additives, updating a previous review.MethodsWe gathered additives policy data from available online sources of tobacco control policies including parties’ reports to the WHO Framework Convention on Tobacco Control (where WHO refers to World Health Organization), the website Tobacco Control Laws, government websites, searches with the Google search engine and consultations with the WHO to ensure comprehensiveness of the assessment. The policies were classified according to their objective and characteristics: Labelling regulations, sales bans and tobacco product design regulations. We classified and organised the regulations according to their stated intent.ResultsWe found that 62 countries had tobacco products’ additives-related regulations at the regional, national or subnational levels. Most of these regulations focused on flavouring additives especially bans on the selling, importing and manufacturing tobacco products with characterising flavours.ConclusionsThe data demonstrate various global policies addressing additives and/or flavours and a range of definitions of additives and flavours. Establishing common definitions and standards could facilitate cooperation between countries and regions.
An Updated Survey of Trends in the Surgical Management of Thumb Carpometacarpal Arthritis – The Increasing Popularity of the Suture Suspension Arthroplasty
Authors: WANG William L. , NEAL William H. E. , YANG S. Steven 
Published: October 2024

Background: The purpose of this study was to conduct an updated survey of American Society for Surgery of the Hand (ASSH) membership to evaluate current preferences for surgical management of thumb CMC arthritis. Past surveys have demonstrated LRTI to be the most preferred surgical technique. We hypothesised that current surgical preferences for thumb CMC arthritis have changed over the last several years due to rising popularity of high-strength suture implants. Methods: A 22-question survey inquired about the preferences for the surgical management of basal joint arthritis and was sent to the ASSH membership. Descriptive statistics were calculated on all survey questions. Chi-squared analysis was used to compare differences in thumb CMC arthroplasty preferences across respondents. Results: A total of 1,499 responses were available for analysis, yielding a response rate of 29.9%. For surgical management of basal joint arthritis in the primary setting, the largest percentage of respondents preferred open trapeziectomy with suture suspension arthroplasty (39.2%); amongst them, over half (56%) used a high-strength suture implant. This was followed by open trapeziectomy with LRTI (38.3%). In the revision setting, most respondents preferred open trapeziectomy with suture suspension arthroplasty (53.5%), followed by LRTI (24.6%). In determining the choice of procedure, respondents felt some form of metacarpal suspension and implant cost to be more important factors than ligament reconstruction and interposition. A higher proportion of international members (16.2%) utilised implant arthroplasty than US/Canadian members (1.1%; p < 0.01). Conclusions: Past surveys have demonstrated LRTI to be the most preferred surgical technique. The current survey demonstrates open trapeziectomy and suture suspension arthroplasty, especially using high-strength suture implants, gaining popularity amongst surgeons, while open trapeziectomy and LRTI decreasing in preference. Suture suspension arthroplasty is now the preferred surgical technique in both the primary and revision setting. Level of Evidence: Level IV (Therapeutic)
Ultrasonographic Evaluation of Flexor Pollicis Longus Tendon Location in Various Functional Hand Positions
Authors: RATANAKOOSAKUL Warot , ANANTAVORASAKUL Navapong , SIRIPOONYOTHAI Sopinan , KITTITHAMVONGS Piyabuth , MALUNGPAISHROPE Kanchai , UERPAIROJKIT Chairoj 
Published: October 2024

Background: Flexor pollicis longus (FPL) tendon injury is a significant complication following distal radius fractures treated with volar locking plate fixation. We were unable to find any studies investigating the FPL tendon in relation to the distal radius in various functional hand positions. The aim of this study is to comprehensively evaluate FPL tendon location in essential functional hand positions commonly encountered in daily life, including pulp pinch, key pinch, chuck grip, power grip, cylindrical grasp and spherical grasp. Methods: We assess the position of the FPL tendon and finger flexor tendons concerning the radius in various functional hand positions. Sixty-two wrists in 31 healthy volunteers were examined using transverse ultrasonography at the watershed area of the radius in six different functional hand positions, including pulp pinch, key pinch, chuck grip, power grip, cylindrical grasp and spherical grasp. Results: The shortest distance between the FPL tendon and radius was observed in the key pinch position with a mean of 3.37 mm, while the cylindrical grasp position showed the farthest distance with a mean of 4.21 mm. Conclusions: The location of the FPL tendon and finger flexor tendons varies across different functional hand positions. Our study shows that these tendons are closest to the radius when the hand is in the key pinch position. Level of Evidence: Level IV (Diagnostic)
Targeting NAD+ Metabolism Vulnerability in FH-Deficient Hereditary Leiomyomatosis and Renal Cell Carcinoma with the Novel NAMPT Inhibitor OT-82
Authors: Najera Susana S. , Ricketts Christopher J. , Schmidt Laura S. , Medina Julia I. , Saito Keita , Ileva Lilia , Brender Jeffrey R. , James Amy M. , Peer Cody J. , Gouker Brad , Karim Baktiar O. , Chernova Olga , Wells Catherine , Wei Ming-Hui , Yang Youfeng , Zhang Xiaohu , Klumpp-Thomas Carleen , Travers Jameson , Chen Lu , Wilson Kelli M. , Issaq Sameer H. , Figg William D. , Difilippantonio Simone , Kalen Joseph D. , Krishna Murali C. , Thomas Craig J. , Ceribelli Michele , Heske Christine M. , Crooks Daniel R. , Meier Jordan L. 
Published: October 2024

Abstract
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited cancer syndrome caused by germline pathogenic variants in the fumarate hydratase (FH) gene. Affected individuals are at risk for developing cutaneous and uterine leiomyomas and aggressive FH-deficient renal cell carcinoma (RCC) with a papillary histology. Due to a disrupted tricarboxylic acid cycle, FH-deficient kidney cancers rely on aerobic glycolysis for energy production, potentially creating compensatory metabolic vulnerabilities. This study conducted a high-throughput drug screen in HLRCC cell lines, which identified a critical dependency on nicotinamide adenine dinucleotide (NAD), a redox cofactor produced by the biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT). Human HLRCC tumors and HLRCC-derived cell lines exhibited elevated NAMPT expression compared with controls. FH-deficient HLRCC cells, but not FH-restored HLRCC or normal kidney cells, were sensitive to NAMPT inhibition. HLRCC cell line viability was significantly decreased in both 2D and 3D in vitro cultures in response to the clinically relevant NAMPT inhibitor OT-82. NAMPT inhibition in vitro significantly decreased the total amount of NAD+, NADH, NADP, NADPH, and poly-ADP-ribose levels, and the effects of NAMPT inhibition could be rescued by the downstream NAD precursor nicotinamide mononucleotide (NMN), confirming the on-target activity of OT-82. Moreover, NAMPT inhibition by OT-82 in two HLRCC xenograft models resulted in severely reduced tumor growth. OT-82 treatment of HLRCC xenograft tumors in vivo inhibited glycolytic flux as demonstrated by reduced lactate/pyruvate ratio in hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging experiments. Overall, our data define NAMPT inhibition as a potential therapeutic approach for FH-deficient HLRCC-associated RCC.
Abstract 54: The kidney-OVLT axis in renovascular hypertension: Individual and combined effects of afferent renal denervation and OVLT lesion in 2K1C rats.
Authors: Ruiz Lauar Mariana , Collister John , Evans Louise , Osborn John 
Published: October 2024

We have recently reported that afferent renal denervation (ARDN) markedly attenuates the pathogenesis of hypertension in the 2 kidney 1 clip (2K1C) model in the rat. This was associated with a reduction in neurogenic pressor activity (NPA). We have also recently shown that lesion of the organum vasculosum of the lamina terminalis (OVLT), a forebrain circumventricular organ, had nearly identical effects in 2K1C rats as ARDN. Together these findings suggest that a neural pathway from the kidney to the OVLT plays an important role in 2K1C hypertension. Based on these findings we hypothesized that the combined effect of ARDN and lesion of the OVLT (OVLTx) on arterial pressure in 2K1C rats would not be greater than the individual treatments.
Male Sprague-Dawley rats were randomly selected to receive either OVLT lesion (x) or sham-OVLTx. One week later, rats were instrumented with telemeters to measure mean arterial pressure (MAP). One week later, renal artery stenosis was created by placing a clip on the left renal artery and then, rats were subjected to ARDN by periaxonal capsaicin or sham treatment of the clipped kidney creating 4 experimental groups: sham+sham (n=6), sham+ARDN (n=6), OVLTx+sham (n=5), OVLTx+ARDN (n=5). MAP was measured daily for 28 days, and at the end of the protocol, NPA was assessed by measuring the peak MAP response to ganglionic blockade.
MAP was similar in all 4 groups at the beginning of the study averaging 108±3 mmHg. MAP increased to 180±10 mmHg in the sham+sham group compared to 130±13mmHg in sham+ARDN, 142±18mmHg in OVLTx+sham rats and 158±14mmHg in OVLTx+ARDN rats (p<0.001). NPA in Sham+sham rats was significantly higher (-44 ± 8 mmHg) compared to sham+ARDN (-18 ± 3 mmHg), OVLTx+sham (-21 ± 2 mmHg) and OVLTx+ARDN (-19 ± 4 mmHg) rats (p<0.05). Notably, the combined effects of OVLTx+ARDN on MAP and NPA were not significantly different from either OVLTx (p=1.00 and p=0.819) or ARDN (p=0.113 and p= 0.878) alone.
In summary, ARDN and OVLTx attenuated hypertension and NPA similarly in 2K1C-HTN rats but the combination of these treatments did not produce any additional effect on MAP or NPA. These findings are consistent with the hypothesis that afferent renal nerves and the OVLT are linked in a common neural pathway required for the development of hypertension following renal artery stenosis.
Abstract 75: CTCF and Rad21 Mediated Regulation of Gene Expression in Human-Induced Pluripotent Stem Cells-derived Endothelial Cells
Authors: Ray Atrayee , Pandey Rajan , Stelloh Cary , Liu Pengyuan , Liu Yong , Kwitek Anne , Geurts Aron , Cowley Allen , Greene Andrew , Liang Mingyu , Rao Sridhar 
Published: October 2024

Blood pressure (BP)-relevant non-coding SNPs identified by GWAS may influence the expression of distal protein-coding genes. Our previous study detected 195 SNPs (out of 26585) in CTCF-binding sites. CTCF and Cohesin are known to modulate cell-type-specific gene expression from a distance by forming chromatin loops. We hypothesized that both may regulate gene expression in BP-relevant cell types. To test this, we depleted CTCF and Rad21 (Cohesin subunit) in human induced pluripotent stem cells-derived endothelial cells (iEC) and performed genome-wide transcriptomic analysis.
We detected 366 and 4184 differentially expressed genes (DEGs) in CTCF and Rad21 depleted iEC (CTCF-/Rad21-KD-iEC) compared to iEC control, respectively. Among them, 111 DEGs are common between the CTCF-KD and Rad21-KD-iEC, though majority showed opposite regulatory effects (Figure 1A). We found 5619 DEGs in the CTCF-KD vs Rad21-KD-iEC (Figure 1B). Pathway analysis detected elevated cell cycle (G2M checkpoint), DNA replication (E2F targets), and repair pathways in Rad21-KD compared to the CTCF-KD-iEC. Rad21 plays an important role in chromosome partitioning and repair, so its depletion may cause dysregulation of these pathways. While the CTCF-KD-iEC showed enrichment of the Epithelial-to-mesenchymal transition (EMT), inflammatory (IFN-gamma, IFN-alpha), and hypoxia pathways (Figure 1C). As CTCF maintains the chromosome boundaries, CTCF-KD may affect chromatin compactness and trigger abnormal gene expression related to these pathways.
In conclusion, our study detected different effects of depletion of CTCF and Rad21 on gene expression in a BP-relevant cell type. The findings provide a basis to explore the role of chromatin looping in BP-relevant gene regulation.
Abstract 76: CASC15 lncRNA as a Mediator of Vascular Senescence in the Renin-Angiotensin System
Authors: Cunha Warlley , Martin Maria , Ahmed Ibrahim , Gomez Delphine , Espinosa-Diez Cristina 
Published: October 2024

The renin-angiotensin system (RAS) regulates vascular function and maintains blood pressure homeostasis. Angiotensin-II (Ang-II) and angiotensin-1-7 (Ang-1-7) have opposing effects on vascular health. Ang-II promotes vascular senescence and pathophysiological remodeling by inducing oxidative stress, inflammation, vascular hypertrophy, and endothelial dysfunction. In contrast, Ang-1-7, known for its vasodilatory, anti-inflammatory, and antioxidative properties, counteracts these detrimental effects, enhancing endothelial function, reducing oxidative stress, and inhibiting inflammation.
Our laboratory has identified the long non-coding RNA CASC15 as a critical regulatory element within the RAS. CASC15 expression is significantly repressed by Ang-II in aortic vascular smooth muscle cells (SMCs), showing a 59.25% decrease compared to the vehicle control (n=10, p=0.000333). Loss of CASC15 induces cellular senescence, increasing senescent cells from a mean of 14.09% (control inhibitor, n=9, SEM=4.824) to 57.79% (CASC15 inhibitor, n=9, SEM=6.420, p<0.0001), and leads to vascular hypertrophy, with cell area increasing from a mean of 46.89% (control inhibitor, n=8, SEM=9.229) to 221.2% (CASC15 inhibitor, n=9, SEM=67.53, p=0.0300).
We hypothesize that CASC15 repression by Ang-II (1 µM) contributes to vascular senescence and increased DNA damage, while Ang-1-7 (1 µM) preserves CASC15 expression and mitigates these effects. Pro-senescent stressors like hydrogen peroxide and doxorubicin also repress CASC15 expression in SMCs. Using RT-qPCR, we observed decreases in CASC15 expression by 29.56% (hydrogen peroxide vs. vehicle, n=4, p=0.0790) and 44.09% (doxorubicin vs. vehicle, n=3, p=0.0733). Ang-1-7 alone did not significantly change CASC15 expression, but combined with Ang-II, it showed potential recovery from 40% repression to 94% recovery. Further research is needed. Immunofluorescence against gamma-H2AX revealed increased DNA damage in SMCs lacking CASC15, with positive foci increasing from 26.27% (control inhibitor, n=4, SEM=1.459) to 63.71% (CASC15 inhibitor, n=4, SEM=1.806, p=0.0009).
In conclusion, CASC15 is a crucial regulator within the RAS. Its repression by Ang-II promotes vascular senescence, hypertrophy, and DNA damage, effects countered by Ang-1-7. Targeting CASC15 could offer new strategies for mitigating vascular aging and improving vascular health, particularly in chronic kidney disease.
Abstract MP12: Reproducibility of White Coat Hypertension and White Coat Uncontrolled Hypertension Among U.S. Adults
Authors: Giacona John , Rugovac Adzona , Kotamraju Manasa , Sundaram Venkatraghavan , Gates Jay , Vazquez Miguel , Vongpatanasin Wanpen 
Published: October 2024

White coat hypertension (WCH) and white coat uncontrolled hypertension (WUCH) are phenomenon characterized by uncontrolled office blood pressures (BP) in the presence of normal out-of-office BPs among untreated and treated individuals, respectively. Although prior studies have investigated the reproducibility of WCH and WUCH, they were mainly limited to non-U.S. adults.
We assessed white coat status in 272 (75% treated) adults with elevated office BP(≥130/80 mmHg) who had home BP (HBP) measurements for three consecutive months without initiation or intensification of antihypertensive medications during the three-month time interval of interest. HBP measurements were included only when number of readings were ≥12/month. WCH and WUCH was defined as HBP≤130/80 mmHg in untreated and treated adults, respectfully. The reproducibility was assessed using the Kappa coefficient (K) with 95% confidence intervals (CI).

Mean age was 76±5 years (57% women, 12% Black adults). WCH was found in 39 of the 68 untreated adults with elevated office BP. WCH adults had an average home BP of 118/72±8/5 mmHg after the initial month of HBP monitoring (HBPM). As shown in
Figure 1
, 87% and 85% had WCH status confirmed on repeat assessment after an additional one- and two-month interval of HBPM (K=0.54 and 0.48, respectfully). WUCH was found in 92 of the 204 treated adults with elevated office BP and had an average home BP of 120/71±5/5 mmHg. Of those, 86% and 84% had WUCH confirmed on repeat assessment after an additional one- and two-month interval of HBPM (K=0.65 and 0.52, respectfully).

In conclusion, WCH and WUCH phenotypes when assessed by home blood pressure monitoring exhibited fair-to-moderate reproducibility among U.S. adults.
Abstract P119: The Heart Failure with Preserved Ejection Fraction Induced By High-Fat Diet and L-NAME in Mice Does not Induce a Renal Damage
Authors: Araos Patricio , Figueroa Stefanny , Arenas Gabriela , Reyes Osorio Javier , Saez Javiera , MOYA JACKELINE , sepulveda Ruth , Rojas Joaquin , Fuenzalida Maria Jose , Gabrielli Luigi , Jalil Jorge , ocaranza Maria Paz , Amador Cristian 
Published: October 2024

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome, without effective therapy, characterized by diastolic dysfunction, a chronic low-grade inflammation and comorbidities such as hypertension. At the present time, few experimental models of HFpEF represent the hallmarks of patients. Recently, it has been described that the administration of a high-fat diet (HFD) in conjunction with an endothelial nitric oxide synthase inhibitor (L-NAME) can adequately reproduce the pathophysiological features of HFpEF. However, the effects on at renal level in HFpEF models have not been fully described. Our goal was to evaluate the kidney damage in a HFpEF model induced by HFD+L-NAME.
Male C57BL/6N mice (12 weeks old, n=4-6) were treated with control diet or HFD (60% in fat calories) plus L-NAME (0.65 g/L in drinking water) for 15 weeks. We evaluated cardiac function (echocardiographic analysis), systolic blood pressure (SBP, plethysmography), cardiac and renal hypertrophy (morphometry and histology), plasma creatinine, blood urea nitrogen (BUN), plasma neutrophil gelatinase-associated lipocalin (pNGAL), proteinuria, and kidney immune cells infiltration (flow cytometry). All data are presented by mean±standard deviation.

After 15 weeks of HFD+L-NAME we observed diastolic dysfunction (p<0.001), an increased SBP (control=128.0±15.3 vs. HFD+L-NAME=155.7±9.8 mmHg; p<0.01), without changes in ejection fraction and shortening fraction. In addition, we did not observe cardiac or renal hypertrophy, nor apparent histological changes in the renal structure between both groups of animals. No differences were found between groups regarding plasma creatinine, pNGAL or BUN, however, we observed that HFD+L-NAME induced proteinuria in compared to control mice (p<0.05). Finally, when we evaluated the immune cells population in kidney of both groups, we observed no differences in dendritic cells, macrophages, or neutrophils. Nevertheless, the HFD+L-NAME treatment was associated to a significant rising of Ly6G
+
CD11b
-
cells population (CD45
+
MHC-II
-
CD11c
+/-
F4/80
-
) compared to control mice (p<0.05).

In conclusion, our results indicate that there is no renal inflammatory damage after 15 weeks of in HFpEF experimental model. However, to our knowledge, an uncharacterized population of Ly6G cells could be participating at this stage which could trigger a long-term renal damage
.

FONDECYT 1221585 (MPO), 1231604 (JJ), 1231909 (CAA), 11241074 (PA) and FONDAP 15130011(MPO, LG).