bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D supplementation modulates autophagy in the pristane-induced lupus model
Authors: dos Santos Manuela , de Souza Silva Jordana Miranda , Bartikoski Bárbara Jonson , Freitas Eduarda Correa , Busatto Amanda , do Espírito Santo Rafaela Cavalheiro , Monticielo Odirlei Andre , Xavier Ricardo Machado 
Published: July 2022

Abstract
Introduction/objectives
Clinical evidence of skeletal muscle involvement is not uncommon in systemic lupus erythematosus (SLE). Because of the poor understanding of signaling pathways involved in SLE muscle wasting, the aim of this study was to evaluate the effects of vitamin D supplementation on skeletal muscle in mice with pristane-induced lupus.

Methods
Balb/c mice with lupus-like disease induced by pristane injection were randomized into three groups: pristane-induced lupus (PIL; n = 10), pristane-induced lupus + vitamin D supplementation (PIL + VD; n = 10) and healthy controls (CO; n = 8). Physical function was evaluated on days 0, 60, 120 and 180. The tibialis anterior and gastrocnemius muscles were collected to evaluate myofiber cross-sectional area (CSA) and protein expression.

Results
The PIL + VD group showed lower muscle strength compared to the CO and PIL groups at different time points. PIL mice showed similar myofiber CSA compared to CO and PIL + VD groups. LC3-II expression was higher in PIL compared to CO and PIL + VD groups. MyoD expression was higher in PIL mice compared to PIL + VD, while myostatin expression was higher in PIL + VD than PIL group. Myogenin expression levels were decreased in the PIL + VD group compared with the CO group. The Akt, p62 and MuRF expressions and mobility assessment showed no significance.

Conclusions
Changes in skeletal muscle in PIL model happen before CSA reduction, possibly due to autophagy degradation, and treatment with Vitamin D has a impact on physical function by decreasing muscle strength and time of fatigue.. Vitamin D supplementation has a potential role modulating physical parameters and signaling pathways in muscle during pristane-induced lupus model.
Diffusion-weighted magnetic resonance imaging in differentiation between different vertebral lesions using ADC mapping as a quantitative assessment tool
Authors: Allam Khaled Essmat , Abd Elkhalek Yasser Ibrahim , Hassan Hend Galal Eldeen Mohamed Ali , Emara Mostafa Abd Elhalim 
Published: July 2022

Abstract
Background
Diffusion-weighted imaging is one of the most useful clinical MRI techniques. Including this technique with other sequences used for routine spine scanning improves sensitivity and the capacity to characterize lesions. This study aims to evaluate the utility of apparent diffusion coefficient obtained from diffusion-weighted MR imaging in differentiating between benign and malignant vertebral lesions according to the optimal cutoff ADC value.

Results
This study included 30 patients at Ain Shams University hospitals; all of them were subjected to full clinical assessment and magnetic resonance imaging. Patients were classified into 4 groups: inflammatory lesions (12 cases) followed by malignant lesions (7 cases), then benign neoplastic lesions (6 cases), then traumatic lesions (3 cases) and osteoporosis (two cases). Inflammatory lesions revealed restricted diffusion. Benign neoplastic lesions/hemangioma showed low signal at DWIs due to free diffusion, while malignant/metastatic lesions showed restricted diffusion. Traumatic lesions showed restricted diffusion. The osteoporotic lesions showed iso- to hyper-intense signal at DWIs. The mean ADC value of the benign lesions was 1.8 ± 0.43 mm2/s, while metastatic tumors was 0.96 ± 0.5 × 10–3 mm2/s; however, overlapping values may be present.

Conclusions
Compared with benign tumors, malignant tumors have lower ADC values; nevertheless, some lesions, such as tuberculosis, have low ADC values that are like those of malignant tumors. Diffusion MRI and ADC values should always be analyzed in conjunction with standard MRI sequences as well as a thorough clinical history and examination.
Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study
Authors: Ossa Gomez Carlos Andrés , Achatz Maria Isabel , Hurtado Mabel , Sanabria-Salas María Carolina , Sullcahuaman Yasser , Chávarri-Guerra Yanin , Dutil Julie , Nielsen Sarah M. , Esplin Edward D. , Michalski Scott T. , Bristow Sara L. , Hatchell Kathryn E. , Nussbaum Robert L. , Pineda-Alvarez Daniel E. , Ashton-Prolla Patricia 
Published: July 2022

PURPOSE To report on pathogenic germline variants detected among individuals undergoing genetic testing for hereditary breast and/or ovarian cancer (HBOC) from Latin America and compare them with self-reported Hispanic individuals from the United States. METHODS In this cross-sectional study, unrelated individuals with a personal/family history suggestive of HBOC who received clinician-ordered germline multigene sequencing were grouped according to the location of the ordering physician: group A, Mexico, Central America, and the Caribbean; group B, South America; and group C, United States with individuals who self-reported Hispanic ethnicity. Relatives who underwent cascade testing were analyzed separately. RESULTS Among 24,075 unrelated probands across all regions, most were female (94.9%) and reported a personal history suggestive of HBOC (range, 65.0%-80.6%); the mean age at testing was 49.1 ± 13.1 years. The average number of genes analyzed per patient was highest in group A (A 63 ± 28, B 56 ± 29, and C 40 ± 28). Between 9.1% and 18.7% of patients had pathogenic germline variants in HBOC genes (highest yield in group A), with the majority associated with high HBOC risk. Compared with US Hispanics individuals the overall yield was significantly higher in both Latin American regions (A v C P = 1.64×10–9, B v C P < 2.2×10–16). Rates of variants of uncertain significance were similar across all three regions (33.7%-42.6%). Cascade testing uptake was low in all regions (A 6.6%, B 4.5%, and C 1.9%). CONCLUSION This study highlights the importance of multigene panel testing in Latin American individuals with newly diagnosed or history of HBOC, who can benefit from medical management changes including targeted therapies, eligibility to clinical trials, risk-reducing surgeries, surveillance and prevention of secondary malignancy, and genetic counseling and subsequent cascade testing of at-risk relatives.
Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial
Authors: Fornecker Luc-Matthieu , Lazarovici Julien , Aurer Igor , Casasnovas René-Olivier , Gac Anne-Claire , Bonnet Christophe , Bouabdallah Krimo , Feugier Pierre , Specht Lena , Molina Lysiane , Touati Mohamed , Borel Cécile , Stamatoullas Aspasia , Nicolas-Virelizier Emmanuelle , Pascal Laurent , Lugtenburg Pieternella , Di Renzo Nicola , Vander Borght Thierry , Traverse-Glehen Alexandra , Dartigues Peggy , Hutchings Martin , Versari Annibale , Meignan Michel , Federico Massimo , André Marc ,   for the LYSA-FIL-EORTC Intergroup
Published: July 2022

PURPOSE The prognosis of patients with early-stage unfavorable Hodgkin lymphoma remains unsatisfactory. We assessed the efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) in previously untreated, early-stage unfavorable Hodgkin lymphoma (ClinicalTrials.gov identifier: NCT02292979 ). METHODS BREACH is a multicenter, randomized, open-label, phase II trial. Eligible patients were age 18-60 years with ≥ 1 unfavorable EORTC/LYSA criterion. Patients were randomly assigned (2:1) to four cycles of BV-AVD or standard doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD), followed by 30 Gy involved node radiotherapy. The primary end point was the positron emission tomography (PET) response rate after two cycles by expert independent review using the Deauville score. The study was designed to test if the PET-negative rate after two cycles of BV-AVD was superior to 75%. We hypothesized a 10% increase in the PET-negative rate after two cycles of BV-AVD. RESULTS Between March 2015 and October 2016, 170 patients were enrolled. After two cycles, the primary end point of the study was met: 93 (82.3%; 90% CI, 75.3 to 88.0) of 113 patients in the BV-AVD arm were PET-negative (Deauville score 1-3) compared with 43 (75.4%; 90% CI, 64.3% to 84.5%) of 57 in the ABVD arm. The 2-year progression-free survival (PFS) was 97.3% (95% CI, 91.9 to 99.1) and 92.6% (95% CI, 81.4% to 97.2%) in the BV-AVD and ABVD arms, respectively. High total metabolic tumor volume was associated with a significantly shorter PFS (hazard ratio, 17.9; 95% CI, 2.2 to 145.5; P < .001). For patients with high total metabolic tumor volume, the 2-year PFS rate was 90.9% (95% CI, 74.4 to 97.0) and 70.7% (95% CI, 39.4% to 87.9%) in the BV-AVD and ABVD arms, respectively. CONCLUSION BV-AVD demonstrated an improvement in the PET-negative rate compared with ABVD after two cycles.
Phase II Study of Enzalutamide for Patients With Androgen Receptor–Positive Salivary Gland Cancers (Alliance A091404)
Authors: Ho Alan L. , Foster Nathan R. , Zoroufy Alex J. , Campbell Jordan D. , Worden Francis , Price Katharine , Adkins Douglas , Bowles Daniel W. , Kang Hyunseok , Burtness Barbara , Sherman Eric , Morton Roscoe , Morris Luc G.T. , Nadeem Zaineb , Katabi Nora , Munster Pamela , Schwartz Gary K. 
Published: July 2022

PURPOSE The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC. METHODS Patients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety. RESULTS Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR– (6 of 13 [46.2%]) or human epidermal growth factor receptor 2–targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide. CONCLUSION Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.
Circulating 1,5-Anhydroglucitol as a Biomarker of ß-cell Mass Independent of a Diabetes Phenotype in Human Subjects
Authors: Jiménez-Sánchez Cecilia , Mezza Teresa , Sinturel Flore , Li Lingzi , Di Giuseppe Gianfranco , Quero Giuseppe , Jornayvaz François R , Guessous Idris , Dibner Charna , Schrauwen Patrick , Alfieri Sergio , Giaccari Andrea , Maechler Pierre 
Published: July 2022

Abstract

Context
During an asymptomatic prediabetic state, the functional ß-cell mass decreases to a critical threshold, triggering diabetes and related symptoms. To date, there are no reliable readouts able to capture in vivo a potential drop of the ß-cell mass.

Objective
Beside its use as a short-term marker of glycemic control, the deoxyhexose 1,5-anhydroglucitol was identified in rodents as a circulating biomarker of the functional ß-cell mass already in the asymptomatic prediabetic stage. The present study investigated the putative corresponding relevance of circulating 1,5-anhydroglucitol in different human cohorts.

Methods
We analyzed clinical and blood parameters in patients with established type 2 diabetes and subjects considered at high risk of developing diabetes, as well as patients with no history of diabetes scheduled for pancreaticoduodenectomy.

Results
Circulating 1,5-anhydroglucitol was reduced in type 2 diabetic patients, negatively correlating with fasting plasma glucose (P &lt; 0.0001) and hemoglobin A1c (P &lt; 0.0001). In healthy subjects, 1,5-AG levels positively correlated with body mass index (P = 0.004) and Homeostatic Model Assessment of Insulin Resistance %S (P &lt; 0.03) and was particularly high in nondiabetic obese individuals, potentially accounting for compensatory ß-cell expansion. Patients with no history of diabetes undergoing pancreaticoduodenectomy exhibited a 50% reduction of circulating 1,5-anhydroglucitol levels following surgery leading to an acute loss of their ß-cell mass (P = 0.002), regardless their glucose tolerance status.

Conclusion
In summary, plasma concentration of 1,5-anhydroglucitol follows the ß-cell mass and its noninvasive monitoring may alert about the loss of ß cells in subjects at risk for diabetes, an event that cannot be captured by other clinical parameters of glycemic control.
Is It Only a Numbers Game? A Macro-Level Study of Educational Hypogamy
Authors: Han Sinn Won 
Published: July 2022

Abstract
In many countries, the tendency for highly educated women to marry down in education has markedly increased. Research has pointed to an oversupply of highly educated women—that is, a marriage squeeze affecting women—as the core reason for this phenomenon. This study aims to provide a more comprehensive understanding of the causes of this marriage trend by analyzing over-time data drawn from IPUMS International census microdata samples for 34 countries. Several key findings are notable. First, the degree of educational hypogamy is associated with the magnitude of the deficit in college-educated men in the marriage market, which is consistent with the marriage squeeze hypothesis. Second, the degree of educational hypogamy is related to the economic empowerment of college-educated women, even after accounting for the mating squeeze effect. Third, counterfactual simulations show that while the mating squeeze is the major driver of educational hypogamy in the majority of the sample countries, the economic empowerment of college-educated women plays an equally important role in several countries.
The Contribution of Price Growth to Pharmaceutical Revenue Growth in the United States: Evidence from Medicines Sold in Retail Pharmacies
Authors: Kakani Pragya , Chernew Michael , Chandra Amitabh 
Published: July 2022

Abstract
Context: To what extent does pharmaceutical revenue growth depend on new medicines versus increasing prices for existing medicines? Moreover, does using list prices, as is commonly done, instead of prices net of confidential rebates offered by manufacturers, which are harder to observe, change the relative importance of the sources of revenue growth?
Methods: This study uses data from SSR Health LLC to address these research questions using decomposition methods that analyze list prices, prices net of rebates, and sales for branded pharmaceutical products sold primarily through retail pharmacies.
Findings: From 2009 to 2019, retail pharmaceutical revenue growth was primarily driven by new products rather than by price increases on existing products. Failing to account for confidential rebates creates a more prominent role for price increases in explaining revenue growth, because list price inflation during this period was 10.9%, whereas net price inflation was 3.3%.
Conclusions: Policies that restrict price growth on existing medicines likely need to be coupled with policies that reduce launch prices to have a meaningful long-term impact on pharmaceutical revenue growth. Using pharmaceutical list prices is often an inadequate approximation for net prices because the role of rebates has increased and varies by drug class.
Reduction in Medicaid Rebates Paid by Pharmaceutical Manufacturers for Outpatient Infused, Injected, Implanted, Inhaled, or Instilled Drugs: The 5i Loophole
Authors: Dickson Sean , Gabriel Nico , Gellad Walid , Hernandez Inmaculada 
Published: July 2022

Abstract
Context: When nonretail pharmacy sales exceed 70% of sales, manufacturers of infused, injected, implanted, inhaled, or instilled (5i) drugs are required to calculate average manufacturer price (AMP) under a different methodology than that used for drugs predominantly distributed through retail channels. Specifically, the modified methodology includes pharmacy benefit manager (PBM) rebates in the calculation of AMP for 5i drugs. The modified methodology reduces manufacturers' Medicaid rebate liability and increases net costs to the Medicaid program.
Methods: The authors identified 15 5i drugs predominantly dispensed through the nonretail setting. Using 2013–2017 data from Medicaid, Medicare, SSR Health, and 340B program eligibility, they estimated differences in AMP, Medicaid rebates, and net Medicaid costs under both the standard and 5i AMP methodologies.
Findings: AMP was 42% lower, on average, under the 5i methodology than under the standard methodology. From 2013–2017, Medicaid rebates under the 5i methodology were 82% lower than under the standard methodology, resulting in manufacturers of these 15 drugs reducing their Medicaid rebate liability by $1.1 billion in five years.
Conclusions: Inclusion of PBM rebates in the calculation of AMP for 5i drugs significantly reduced Medicaid rebates, resulting in higher Medicaid spending. This may incentivize manufacturers to shift sales to nonretail channels. To remove this incentive, policy makers should consider excluding PBM rebates from the calculation of AMP for 5i drugs.
Exercise-Induced Fatigue in Hamstring versus Quadriceps Muscles and Consequences on the Torque–Duration Relationship in Men
Authors: MASSAMBA ANASTHASE , HUCTEAU ELYSE , MALLARD JORIS , DUCROCQ GUILLAUME P. , FAVRET FABRICE , HUREAU THOMAS J. 
Published: July 2022

ABSTRACT

Purpose
The present study investigated the mechanisms of neuromuscular fatigue in quadriceps and hamstring muscles and its consequences on the torque–duration relationship.

Methods
Twelve healthy men performed a 5-min all-out exercise (3-s contraction, 2-s relaxation) with either quadriceps or hamstring muscles on separate days. Central fatigue and peripheral fatigue were quantified via changes in pre- to postexercise voluntary activation (VA) and potentiated twitch (PTw) torque evoked by supramaximal electrical stimulation, respectively. Critical torque was determined as the mean torque of the last six contractions, whereas W′ was calculated as the torque impulse done above critical torque.

Results
After exercise, maximal voluntary contraction (MVC) decreased to a greater magnitude (P < 0.001) in quadriceps (−67% ± 9%) compared with hamstring (−51% ± 10%). ∆PTw was also greater in quadriceps compared with hamstring (−69% ± 15% vs 55% ± 10%, P < 0.01), whereas central fatigue only developed in quadriceps (∆VA, −25% ± 28%). Hamstring demonstrated reduced critical torque compared with quadriceps (60 ± 12 vs 97 ± 26 N·m, P < 0.001) as well as drastically lower W′ (1001 ± 696 vs 8111 ± 2073 N·m·s, P < 0.001). No correlation was found between quadriceps and hamstring for any index of neuromuscular fatigue (∆MVC, ∆PTw, or ∆VA).

Conclusions
These findings revealed that hamstring presented different etiology and magnitude of neuromuscular fatigue compared with quadriceps. The absence of correlation observed between quadriceps and hamstring fatigue parameters (∆MVC, ∆PTw, or ∆VA) suggests no interrelation in fatigue etiology between these two muscle groups within individuals and, therefore, highlights the need to investigate specifically hamstring muscle fatigue.
Covid-19 associated shoulder girdle calcific myositis: a novel entity
Authors: Al-Khudairi Naji , Dulay Gurdeep S , Witham Fiona 
Published: July 2022

Objective: To investigate the prevalence, describe the radiological features, and consider the clinical sequelae of COVID-19- associated shoulder girdle calcific myositis. Methods: All patients who underwent a CT pulmonary angiogram study at our institution (Queen Alexandra Hospital, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom) in April and May 2020, January 2021, and July 2021 were included. A total of 1239 CT pulmonary angiogram studies for 1201 patients were reviewed. Patients with COVID-19 and associated shoulder girdle calcific myositis were identified. Their electronic patient records were reviewed. The patients’ demographics, serum inflammatory markers, and proning history were recorded. Results: Of the 364 patients in Wave 1, 71 patients (19.5%) had COVID-19, and of those, 2 patients (2.8%) had shoulder girdle calcific myositis. Of the 521 patients in Wave 2, 354 patients (67.9%) had COVID-19, and of those, 3 patients (0.8%) had shoulder girdle calcific myositis. Of the 316 patients in Wave 3, 37 patients (11.7%) had COVID-19, and of those, 1 patient (2.7%) had shoulder girdle calcific myositis. The overall prevalence was 1.3%. The most common site of calcific myositis was within the subscapularis muscle. Conclusion: COVID-19-associated shoulder girdle calcific myositis is a rare extrapulmonary musculoskeletal manifestation of COVID-19. Early recognition and increased awareness of this disease entity, in our experience, aids in reducing patient morbidity and improving long-term functional outcome. Advances in knowledge: We have reported a novel disease entity associated with COVID-19, in the form of shoulder girdle calcific myositis. We have described the common imaging features and discussed our experience of management and clinical sequelae.