bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of off‐label use regulations on patient care in dermatology – a prospective study of cost‐coverage applications filed by tertiary dermatology clinics throughout Germany
Authors: Werner R.N. , Pennitz A. , Eisert L. , Schmidle P. , Zink A. , Abraham S. , Schäkel K. , Wolff I. , Goebeler M. , Plange J. , Sollfrank L. , Zielbauer S. , Koll P. , Amschler K. , Müller V. , Nast A. 
Published: June 2022

AbstractBackgroundIn dermatology, a medical speciality with a relatively high number of rare diseases, physicians often have to resort to off‐label treatment options. To avoid claims, physicians in Germany can file a cost‐coverage request (off‐label application, OL‐A).ObjectivesOur aim was to investigate the extent to which the current regulations affect patient care.Material and methodsProspective cohort study among tertiary dermatology clinics throughout Germany, consecutively including OL‐As (05/2019–09/2020) and assessing the follow‐up correspondence. We modelled regressions to assess factors associated with cost‐coverage decisions and the time needed by health insurers to process the OL‐As.ResultsThirteen clinics provided data on 121 OL‐As, two of which applied for on‐label treatments. Of the remaining 119 OL‐As, 70 (58.8%) were immediately approved and 44 (37.0%) rejected. Including cases with one or more appeals, 87 of 119 OL‐As (73.1%) were finally approved and 26 (21.9%) rejected. There was an association of the final approval rate with (1) the class of medication/treatment, with approval rates being significantly lower for JAK inhibitors than for biologics (OR 0.16, 95%‐CI: 0.03–0.82); (2) German state, with approval rates being lower in eastern than in western states (OR 0.30, 95%‐CI 0.12–0.76); and (3) cost of the intervention (no linear trend). However, none of these predictors was significant in our multiple logistic regression models. The median health insurer's processing time (first response) was 29 days (IQR 22–38). Our analyses showed no evidence of an association with the predictors we assessed. In cases approved, the median time from the decision to file an OL‐A to the actual initiation of the treatment was 65.5 days (IQR 51–92).ConclusionsOur study points to substantial delays and inequalities in the provision of timely health care for dermatological patients with rare diseases, often involving treatments for which there is no adequate approved therapy.
Screw‐retained surgical guide for implant placement in terminal dentition patients with existing implants
Authors: Papaspyridakos Panos , De Souza Andre , Kudara Yukio , Basha Vince , Bokhary Abdullah , Sinada Naif , Chochlidakis Konstantinos 
Published: June 2022

AbstractFor patients with existing implants in need of additional implant placement, the use of the existing implants for guide fixation seems to be a logical alternative. Current options for the fabrication of surgical guides involve creating surgical guides that are mucosa‐borne and/or retained by fixation pins. Since these existing techniques involve inherent inaccuracies, the fabrication of surgical guides that are screw‐retained at the implant‐ or abutment‐level would eliminate the introduction of those same fundamental inaccuracies. The purpose of the present technical report is to illustrate a step‐by‐step digitally planned guided implant placement protocol for terminal dentition patients with salvageable existing implants requiring full‐arch implant rehabilitation. The advantages of this protocol include enhancing the accuracy of guided implant placement with screw‐retention versus the traditional mucosa‐ or fixation pin support. Thus, this simplifies the transition from failing teeth to implants by ensuring that fixed provisionalization serves both functional and esthetic requirements. This protocol can also predictably reduce chairside time and adjustments at the surgical implant placement appointment.
GEOCHEMISTRY AND CARBON ISOTOPE CHARACTERISTICS OF ASSOCIATED GASES FROM OILFIELDS IN THE NW GREATER CAUCASUS, RUSSIA
Authors: Oblasov N. V. , Goncharov I. V. , Derduga A. V. , Kunitsyna I. V. 
Published: June 2022

The NW Greater Caucasus and surrounding areas have a long history of petroleum production dating back to the mid‐19th century. However the origin of the oil and gas is still a matter of debate. This paper focusses on a study area to the north of the western Greater Caucasus covering the West and East Kuban Basins and neighbouring structural highs where oil and natural gas occur in reservoir units of Neogene, Paleogene, Cretaceous and Jurassic ages. The study is based on the results of organic geochemical and stable carbon isotope analyses of 21 samples of associated gases from 16 oil fields. The gas samples' compositions were investigated together with the δ13C values of C1 to C5 alkanes. Twenty of the gas samples were of thermogenic origin and one was mixed (thermogenic and secondary microbial). δ13C values for CH4 for all the gas samples varied over a wide range from ‐62.3 to ‐30.0 ‰, indicating major variations in the thermal maturity of the respective source rocks.In a previous study, three genetic types of oil were identified in the study area and are referred to here as Types 1, 2 and 3. Gaseous hydrocarbons associated with Type 1 oils were generated by source rocks in the Middle Eocene Kuma Formation and the Oligocene (lower) part of the Maikop Group which are inferred to have been deposited in anoxic, deep‐marine conditions. C2–C5 alkanes in gases associated with Type 1 oils have the lowest (most negative) δ13C values of the samples studied, and the lowest iso‐butane: n‐butane and iso‐pentane: n‐pentane ratios. These gas samples were recovered from wells in oilfields located in the south and SE of the West Kuban Basin, in the Akhtyrskaya fault zone which extends along the northern flank of the Greater Caucasus foldbelt.Higher δ13C values of C2–C5 alkanes were found in gas samples associated with Type 2 oils which were recovered from wells in the central West Kuban Basin. The associated source rocks are interpreted to have been deposited in weakly oxidizing subaqueous conditions and to contain mainly marine organic matter but with an input of higher land plant material. The precise age and stratigraphic identity of the source rocks is unresolved but they may comprise the Upper Oligocene – Lower Miocene (middle and upper) part of the Maikop Group.In gases associated with Type 3 oils, δ13C values of ethane to pentane are similar to those of gases associated with Type 2 oils. These gases were recovered from wells in oilfields located on the Adygeya Swell which divides the southern East and West Kuban Basins and from the Armavir‐Nevinnomyssk Swell to the north. The precise source of these gases and oils is not known but the oils are probably older than Late Cretaceous on account of the absence of oleanane.
Integration of hotspot identification, gap analysis, and niche modeling supports the conservation of Chinese threatened higher plants
Authors: Xue Tian‐Tian , Yang Xu‐Dong , Liu Qin , Qin Fei , Zhang Wen‐Di , Janssens Steven B. , Yu Sheng‐Xiang 
Published: June 2022

AbstractA significant fraction of higher plants in China are threatened due to dramatic landscape transformation and increasing climate change. However, the conservation effectiveness of threatened higher plants (THPs) and their response to climate change are still underexplored to date. Based on the latest list of THPs in China, we obtained 102 593 occurrence records with latitude and longitude for 3858 THPs. By integrating the distribution patterns of three biodiversity indexes (i.e., species richness, species complementarity, and weighted endemism) and 10 plant categories, we identified hotspots for THPs and calculated the conservation effectiveness of nature reserves. We then selected 1959 THPs to project the shift of species richness and range sizes under climate change (representative concentration pathway [RCP] 2.6 and RCP 8.5). In total, 16 hotspot areas covering 7.38% of Chinese land area and containing 91.73% of THPs were identified. Current nature reserves protected 35.05% of hotspots, 73.07% of all THPs, and 56.64% of narrow‐ranged species. By the 2070s, the species richness of THPs were predicted to decrease in Southeast and Central China, and 42.42% (RCP 2.6) and 51.40% (RCP 8.5) of the 1959 THPs would confront habitat contraction. Future conservation efforts should focus on the conservation gaps and carry out targeted conservation for THPs with narrow distribution range. In order to cope with climate change, the hotspots with relatively low species loss can serve as important areas to contain current species diversity and the areas with high species gain offer opportunities for ex‐situ conservation of THPs.
p53 gene delivery via a recombinant Salmonella enterica Typhimurium leads to human bladder carcinoma cell death in vitro
Authors: Pérez Jorge G. , Módolo D.G. , Jaimes-Florez Y.P. , Fávaro W.J. , de Jesus M.B. , Brocchi M. 
Published: June 2022

Abstract
Numerous studies have attempted to restore the function of the tumour suppressor p53 as an anti-cancer strategy through gene delivery. However, most studies employed non-bacterial vectors to deliver p53. Various facultative and obligate anaerobic bacteria have been proposed as vectors because of their intrinsic tumour targeting ability and anti-tumour activity. Salmonella enterica Typhimurium is the most studied bacterial vector in anti-cancer therapy. We used the previously designed χ11218 strain of S. enterica Typhimurium, displaying regulated delayed lysis, as a vector for delivering p53 to human bladder carcinoma cells, restoring wild-type p53 protein function. We cloned p53 into pYA4545 (containing a eukaryotic expression system) to generate the χ11218 pYA4545p53 strain. Cloning of p53 did not affect the growth or interfere with the invasive and replicative capacity of χ11218 bacteria in tumour cells. Human bladder carcinoma cells (expressing mutated p53) transfected with pYA4545p53 showed a significant increase in the expression of p53 protein. We demonstrated that p53 supplied by χ11218 significantly decreased the viability of human bladder cancer cells in a dose-dependent manner. This study demonstrates the applicability of the attenuated χ11218 strain as a vector for DNA plasmids expressing tumour suppressor genes.
Shift work and the risk for metabolic syndrome among healthcare workers: A systematic review and meta‐analysis
Authors: Sooriyaarachchi Piumika , Jayawardena Ranil , Pavey Toby , King Neil A. 
Published: June 2022

SummaryShift work, defined as work occurring outside typical daytime working hours, is associated with an increased risk for metabolic syndrome (MetS) due to several biological and environmental changes. The MetS refers to the clustering of several known cardiovascular risk factors, including insulin resistance, obesity, dyslipidemia, and hypertension. This systematic review aims to evaluate the literature on the association between shift work and the risk of MetS in employees of the health sector. A systematic search was conducted in PubMed, Web of Science, and Scopus databases using appropriate keywords for studies published before September 1, 2021. Eligible studies were those that compared the prevalence of MetS between day and shift healthcare workers; had a cross‐sectional, case–control, or cohort study design; provided sufficient data for calculating odds ratios or relative risks with 95% confidence intervals; and articles in English. The Joanna Briggs Institute prevalence critical appraisal tool was used for quality analysis. Risk for MetS and related measures of effect size were retrieved from studies for meta‐analysis. Twelve studies met the criteria for inclusion in the review and meta‐analysis. Sample sizes ranged from 42 to 738, and the age range of subjects was between 18 and 65 years. Ten studies demonstrated high methodological quality, while two studies were of average quality. Ten out of 12 studies in the review demonstrated a higher risk in shift workers for developing MetS than day workers. The pooled OR of MetS in shift workers based on 12 studies was 2.17 (95% CI = 1.31–3.60, P = 0.003; I2 = 82%, P < 0.001). Shift workers exhibited more than a twofold increase in the chance of developing MetS in comparison with day workers.
Epidemiological Characteristics of Patients Operated for Achilles Tendon Rupture in Shanghai
Authors: Teng Zhao‐lin , Cao Sheng‐xuan , Ma Xin , Wang Xu , Huang Jia‐Zhang , Zhang Chao , Geng Xiang 
Published: June 2022

ObjectiveTo reflect the potential epidemiological characteristics of Achilles tendon (AT) rupture in Shanghai, China, which has been rarely reported before.MethodsThis work is a descriptive epidemiology study. A total of 302 cases of AT rupture admitted to our department between 01/2013 and 02/2020 are analyzed according to telephone follow‐up and medical records. Male to female ratio is 10.3 and the average age is 37.5 years. The record of each case includes age, gender, Body mass index (BMI), quinolone use, corticoid exposure and related medical history/comorbidities. If the case is sports‐related (SR), details including kind of sports, intensity of exercise, exercise time before rupture, specific action that causes rupture and situation of warm‐up are collected. Two independent sample t‐tests and Pearson chi‐square tests are used for statistical analysis.ResultsA total of 252 ruptures are SR. Male to female ratio is 15.6 in SR cases. Most SR ruptures occur in patients aged 25–39 years. Ball games are major sports responsible for rupture: basketball in 95 (37.7%), badminton in 68 (27.0%) and soccer in 62 (24.6%). Acceleration and running start is the specific action that cause most (37.7%) ruptures. AT cases are observed in 91 patients with warm‐up and 161 without preparation before exercise. As a result, more ruptures happened within 10 min' sports in 161 unprepared (22.4%) than in 91 prepared (5.5%) cases. In SR cases, 107 and 145 cases are observed on weekends and weekdays. Of the 302 total cases, 64 are associated with Achilles tendinopathy. Frequently reported factors such as quinolone use and corticoid exposure are found only in two and 11 of all cases, respectively.ConclusionMiddle‐aged males are common victims of AT rupture in Shanghai. Sports including basketball, badminton, soccer and actions involving in sudden and severe contraction of AT cause most ruptures. Warm‐up before exercise reduces rupture in short time. Factors such as quinolone, corticoid and Achilles tendonitis still need attention.
Extensive Spinal Epidural Abscess Resulting in Complete Paraplegia Treated by Selective Laminectomies and Irrigation
Authors: Xu Tongshuai , Du Yukun , Guo Jianwei , Li Jianyi , Shao Cheng , Shi Changfang , Ren Xianfeng , Xi Yongming 
Published: June 2022

BackgroundSpinal epidural abscess (SEA) is an uncommon clinical entity that is often subject to delayed diagnosis and suboptimal treatment. Untreated disease leads to compression of the spinal cord, resulting in devastating complications.Case PresentationA 56‐year‐old man visited our hospital for progressive lower back and lower extremity pain of several days' duration. Significant pyrexia (39.5°C) and elevated C‐reactive protein (89.2 mg/L) were detected during admission, but no positive neurological examination findings were observed. Magnetic resonance imaging revealed pyogenic discitis at L3–4. Despite the administration of directed antibiotic therapy, the patient's condition rapidly deteriorated, culminating in complete paraplegia secondary to an extensive SEA from L4 to C7. Emergency spinal decompression surgery was canceled due to his poor clinical condition and refusal of informed consent. After further deterioration, he consented to two‐level selective laminectomies and irrigation.ConclusionsIn contrast with prior case reports, this case illustrates the natural history of an extensive SEA during conservative and late surgical treatment. Early diagnosis and timely surgical decompression are of great importance for extensive SEA.
Inborn errors of immunity caused by defects in the DNA damage response pathways: Importance of minimizing treatment‐related genotoxicity
Authors: Fournier Benjamin , Mahlaoui Nizar , Moshous Despina , de Villartay Jean‐Pierre 
Published: June 2022

AbstractSeveral primary immunodeficiencies are caused by defects in the general DNA repair machinery as exemplified by the T‐B‐ radiosensitive SCID condition owing to impaired resolution of programmed DNA double‐strand breaks introduced by RAG1/2 during V(D)J recombination. The genome instability generally associated with these conditions results in an increased propensity to develop malignancies requiring genotoxic‐based anti‐cancer treatments. Moreover, the extent of immune deficiency often calls for hematopoietic stem cell transplantation as a definitive treatment, also requiring genotoxic‐based conditioning regimen prior to transplantation. In both cases, the underlying general DNA repair defect may result in catastrophic iatrogenic consequences. It is, therefore, of paramount importance to assess the functionality of the DNA repair apparatus prior to any genotoxic treatment when the exact molecular cause of the disease is unknown. For this purpose, two simple assays can be used on patients derived peripheral blood lymphocytes: (1) the PROMIDISα biomarker, based on the next‐generation sequencing analysis of the TCRα repertoire, will highlight specific signatures of DNA repair deficiencies; (2) direct analysis of the sensitivity of peripheral lymphocytes to ionizing radiation will formally identify patients at risk to develop toxicity toward genotoxic‐based treatments.
Influence of cross‐sectional area and fat infiltration of paraspinal muscles on analgesic efficacy of epidural steroid injection in elderly patients
Authors: Kim Hee Jung , Rho Miribi , Yoon Kyung Bong , Jo Minju , Lee Dong Woo , Kim Shin Hyung 
Published: June 2022

AbstractBackgroundAn assessment of paraspinal muscle degeneration based on magnetic resonance imaging has been used to investigate both sarcopenia and myosteatosis. The morphologic changes in cross‐sectional area and fat infiltration of the paraspinal muscles can affect pain outcomes after epidural steroid injection.MethodsPatients ≥65 years of age who underwent fluoroscopy‐guided lumbar epidural steroid injections were enrolled. Good analgesia was defined as ≥50% reduction in pain score at 4 weeks after injection. Cross‐sectional area and grade of fat infiltration of the paraspinal muscles on magnetic resonance images at the level of L3–L4 disc were measured. Patient demographics, pain‐related factors, clinical factors, and paraspinal muscle measurements were compared between good and poor analgesia groups. The factors associated with pain outcomes after injection were identified using multivariate analysis.ResultsA total of 245 patients consisting of 149 and 96 patients in the good and poor analgesia groups, respectively, fully satisfied the study criteria for analysis. Patients of older age, opioid use, and high‐grade foraminal stenosis were frequently observed in the poor analgesia group. The grade of fat infiltration of the paraspinal muscles was significantly higher in the poor analgesia group (Grade 2, 20.8% vs. 42.7%, p < 0.001), and this result was predominantly observed in female patients. However, there was no difference in the muscle cross‐sectional area between the two groups (18.29 ± 3.16 vs. 18.59 ± 3.03 cm2/m2, p = 0.460). The percentage of patients with good analgesia decreased as the grade of fat infiltration increased (Grade 0 = 75.0%, Grade 1 = 65.8%, Grade 2 = 43.0%, p < 0.001). Multivariate logistic regression analysis revealed that preinjection opioid use [adjusted odds ratio (aOR) = 1.926, 95% confidence interval (CI) = 1.084–3.422, p = 0.025], moderate to severe foraminal stenosis (aOR = 2.859, 95% CI = 1.371–5.965, p = 0.005), and high‐grade fat infiltration of the paraspinal muscles (aOR = 4.258, 95% CI = 1.805–10.043, p = 0.001) were significantly associated with poor analgesia after injection.ConclusionHigh fat infiltration of the paraspinal muscles at the mid‐lumbar region appeared to be an independent factor associated with poor analgesia after epidural steroid injection in elderly patients with symptomatic degenerative lumbar spinal disease receiving conservative care. However, the cross‐sectional area of the paraspinal muscles was not associated with pain relief after injection.
Monitoring plant water status via static uniaxial compression of the leaf lamina
Authors: Fuenzalida Tomás I. , Binks Oliver , Bryant Callum J. , Wolfe Joe , Ball Marilyn C. 
Published: June 2022

AbstractTurgor pressure is an essential, but difficult to measure indicator of plant water status. Turgor has been quantified by localized compression of cells or tissues, but a simple method to perform these measurements is lacking. We hypothesized that changes in leaf turgidity can be monitored by uniaxially compressing the leaf lamina and measuring the mechanical stress under a constrained thickness (stress relaxation) and that changes in leaf water content can be monitored by measuring the leaf thickness under constant mechanical stress. Using a simple, custom‐built leaf squeeze‐flow rheometer, we performed different compression tests on leaves from 13 plant species. The mechanical stress measured during stress relaxation was correlated with leaf bulk turgor pressure (R2 > 0.95) and thus with balancing pressure (R2 > 0.94); the leaf thickness measured under constant mechanical stress was correlated with relative water content (R2 > 0.74). The coefficients of these relationships were related to the leaf bulk osmotic pressure at the turgor‐loss point. An idealized average‐cell model suggests that, under isothermal conditions, the stationary bulk modulus during compression is largely determined by the bulk osmotic pressure. Our study presents an inexpensive, accessible and automatable method to monitor plant water status noninvasively.
Successful use of telemedicine for evaluation of infantile hemangiomas during the early COVID‐19 pandemic: A cross‐sectional study
Authors: Kittler Nicole W. , Frieden Ilona J. , Abuabara Katrina , Siegel Dawn H. , Horii Kimberly A. , Mathes Erin F. , Blei Francine , Haggstrom Anita N. , Streicher Jenna L. , Metry Denise W. , Garzon Maria C. , Morel Kimberly D. , Lauren Christine T. , Hogeling Marcia , Fernandez Faith Esteban , Baselga Eulalia , Tollefson Megha M. , Newell Brandon D. , McCuaig Catherine C. , Mancini Anthony J. , Chamlin Sarah L. , Becker Emily M. , Cossio Maria L. , Shah Sonal D. 
Published: June 2022

AbstractBackground/ObjectivesThe COVID‐19 pandemic prompted a rapid expansion in the use of telemedicine. This study aimed to assess the experiences of hemangioma specialists utilizing telemedicine during the COVID‐19 pandemic to evaluate and manage infantile hemangiomas (IH), including perceived effectiveness of different modalities and barriers to care delivery.MethodsMulticenter cross‐sectional study asking providers to describe their experiences using telemedicine for initial evaluation of IH from March to September 2020.ResultsThe study included 281 patients from 15 medical centers internationally. Median time from referral to evaluation was 17 days. Median physician confidence in performing evaluations via telemedicine was 95.0 (IQR 90.0–100.0). Most evaluations were performed via video communication with photographs or audio communication with photographs; when not initially available, photographs were requested in 51.4%. Providers preferred follow‐up modalities that included photographs.ConclusionsPhysicians with extensive expertise in managing IH are confident in their abilities to assess and manage IH via telemedicine including initiating treatment in patients without risk factors for beta‐blocker therapy. There was a preference for hybrid modalities that included photographs. The data suggest that telemedicine can be effective for managing IH and may decrease wait times and improve specialist reach to underserved areas.