bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Treatment Outcomes after Collagenase Injection and Percutaneous Needle Fasciotomy for Dupuytren’s Contracture: Objective and Subjective Comparisons with a 3-Year Follow-Up
Authors: Abe Yoshihiro 
Published: June 2020

Background:
This study compared the effectiveness of injectable collagenase clostridium histolyticum and percutaneous needle fasciotomy in the treatment of Dupuytren’s contracture.

Methods:
Patients with a total passive extension deficit of 30 degrees or more in a single digital ray were enrolled and assigned randomly to receive either collagenase clostridium histolyticum injections or percutaneous needle fasciotomy. Preoperative severity of proximal interphalangeal joint contracture for Dupuytren’s disease was classified according to the British Society for Surgery of the Hand as less than 30 degrees (stage I) or 30 degrees or more (stage II).

Results:
Of the 70 patients enrolled, 36 patients with 46 joints received collagenase clostridium histolyticum injections and 34 patients with 48 joints received percutaneous needle fasciotomy. At day 30, successful corrections were obtained in only 50 percent of the injection group and 67 percent of the fasciotomy group for stage II proximal interphalangeal joints. Recurrences were frequent among patients with stage II joint contractures. The mean Quick Disabilities of the Arm, Shoulder and Hand questionnaire score at day 30 was significantly higher in the injection group compared with the fasciotomy group (7.5 versus 4.2, respectively). In the injection group, adverse events were reported for all patients. In the fasciotomy group, complications were reported for 15 percent of patients.

Conclusions:
The collagenase clostridium histolyticum and percutaneous needle fasciotomy groups had similar outcomes for Dupuytren’s contracture with 3 years’ follow-up. Recurrences were frequent among patients with stage II proximal interphalangeal joint contractures. The Unité Rhumatologique des Affections de la Main scale and Quick Disabilities of the Arm, Shoulder and Hand questionnaire score decreased significantly for both groups at final follow-up.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
Volumetric Differences in the Suprafascial and Subfascial Compartments of Patients with Secondary Unilateral Lower Limb Lymphedema
Authors: Chu Sung-Yu , Wang Stewart C. , Chan Wen-Hui , Wang Nicholas , Huang Yen-Ling , Cheng Ming-Huei , Cederna Paul Stephen 
Published: June 2020

Background:
The subfascial compartment (deep to the deep fascia) in extremity lymphedema has not been evaluated. This study investigated the volumetric differences between the suprafascial and subfascial compartments of patients with unilateral lower extremity lymphedema.

Methods:
Thirty-two female patients with unilateral lower extremity lymphedema were enrolled, with eight patients in each of Cheng lymphedema grades I to IV. The volumes of the suprafascial and subfascial compartments were calculated after manually drawing the region of interest on computed tomographic images. The volumetric differences and their ratios in the suprafascial and subfascial compartments between each patient’s bilateral limbs were compared.

Results:
The volume of the lymphedematous limbs (9647 ml) was significantly greater than the volume of unaffected limbs (6906 ml), with a median volumetric difference of 2097 ml (30.6 percent) (p < 0.01). The median suprafascial compartment volumetric difference was 1887 ml (56.6 percent) and the subfascial compartment volumetric difference was 208 ml (4.7 percent) (p < 0.01). The median volumetric difference ratio of the thigh and lower leg was 24.6 percent and 40.6 percent, respectively. The median volumetric differences in Cheng lymphedema grades I to IV were 1012, 1787, 2434, and 4107 ml, respectively, which were statistically significant among the four Cheng lymphedema grades using the Kruskal-Wallis test (p < 0.01).

Conclusions:
The volumetric differences in the lymphedematous limb were statistically significantly greater than in the unaffected limb, including both suprafascial and subfascial compartments. The volumetric differences are consistent with the Cheng lymphedema grading system as a reliable indicator of unilateral extremity lymphedema.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Diagnostic, IV.
The Economic Burden of Out-of-Pocket Expenses for Plastic Surgery Procedures
Authors: Billig Jessica I. , Chen Jung-Sheng , Lu Yu-Ting , Chung Kevin C. , Sears Erika D. 
Published: June 2020

Background:
Health insurance reimbursement structure has evolved, with patients becoming increasingly responsible for their health care costs through rising out-of-pocket expenses. High levels of cost sharing can lead to delays in access to care, influence treatment decisions, and cause financial distress for patients.

Methods:
Patients undergoing the most common outpatient reconstructive plastic surgery operations were identified using Truven MarketScan databases from 2009 to 2017. Total cost of the surgery paid to the insurer and out-of-pocket expenses, including deductible, copayment, and coinsurance, were calculated. Multivariable generalized linear modeling with log link and gamma distribution was used to predict adjusted total and out-of-pocket expenses. All costs were inflation-adjusted to 2017 dollars.

Results:
The authors evaluated 3,165,913 outpatient plastic and reconstructive surgical procedures between 2009 and 2017. From 2009 to 2017, total costs had a significant increase of 25 percent, and out-of-pocket expenses had a significant increase of 54 percent. Using generalized linear modeling, procedures performed in outpatient hospitals conferred an additional $1999 in total costs (95 percent CI, $1978 to $2020) and $259 in out-of-pocket expenses (95 percent CI, $254 to $264) compared with office procedures. Ambulatory surgical center procedures conferred an additional $1698 in total costs (95 percent CI, $1677 to $1718) and $279 in out-of-pocket expenses (95 percent CI, $273 to $285) compared with office procedures.

Conclusions:
For outpatient plastic surgery procedures, out-of-pocket expenses are increasing at a faster rate than total costs, which may have implications for access to care and timing of surgery. Providers should realize the increasing burden of out-of-pocket expenses and the effect of surgical location on patients’ costs when possible.
Photoaged Skin Therapy with Adipose-Derived Stem Cells
Authors: Charles-de-Sá Luiz , Gontijo-de-Amorim Natale Ferreira , Rigotti Gino , Sbarbati Andrea , Bernardi Paolo , Benati Donatella , Bizon Vieira Carias Rosana , Maeda Takiya Christina , Borojevic Radovan 
Published: June 2020

Background:
The major intrinsic cause of facial skin degeneration is age, associated with extrinsic factors such as exposure to sun. Its major pathologic causes are degeneration of the elastin matrix, with loss of oxytalan and elaunin fibers in the subepidermal region, and actinic degeneration of elastin fibers that lose their functional properties in the deep dermis. Therapy using autologous adipose mesenchymal stem cells for regeneration of extracellular matrix in patients with solar elastosis was addressed in qualitative and quantitative analyses of the dermal elastic fiber system and the associated cells.

Methods:
Mesenchymal stem cells were obtained from lipoaspirates, expanded in vitro, and introduced into the facial skin of patients submitted after 3 to 4 months to a face-lift operation. In the retrieved skin, immunocytochemical analyses quantified elastic matrix components; cathepsin K; matrix metalloproteinase 12 (macrophage metalloelastase); and the macrophage M2 markers CD68, CD206, and hemeoxygenase-1.

Results:
A full de novo formation of oxytalan and elaunin fibers was observed in the subepidermal region, with reconstitution of the papillary structure of the dermal-epidermal junction. Elastotic deposits in the deep dermis were substituted by a normal elastin fiber network. The coordinated removal of the pathologic deposits and their substitution by the normal ones was concomitant with activation of cathepsin K and matrix metalloproteinase 12, and with expansion of the M2 macrophage infiltration.

Conclusion:
The full regeneration of solar elastosis was obtained by injection of in vitro expanded autologous adipose mesenchymal stem cells, which are appropriate, competent, and sufficient to elicit the full structural regeneration of the sun-aged skin.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Evaluation ofin vitroactivity of manogepix against multidrug-resistant and pan-resistantCandida aurisfrom the New York Outbreak
Authors: Zhu YanChun , Kilburn Shannon , Kapoor Mili , Chaturvedi Sudha , Shaw Karen Joy , Chaturvedi Vishnu 
Published: June 2020

ABSTRACTAn ongoingCandida aurisoutbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NYC. aurisisolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several isolates are pan-resistant. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug, fosmanogepix, is currently in Phase 2 clinical development for the treatment of fungal infections. We evaluated the susceptibility of 200 New YorkC. aurisisolates to MGX and 10 comparator drugs using CLSI methodology. MGX demonstrated lower MICs than comparators (MIC50and MIC900.03 mg/L; range 0.004-0.06 mg/L). The MGX epidemiological cutoff value (ECV, 99% cutoff) for the testedC. aurisisolates was 0.06 mg/L. MGX was 8-32-fold more active than the echinocandins, 16-64-fold more active than the azoles, and 64-fold more active than amphotericin B. No differences were found in the MGX or comparators’ MIC50, MIC90, or GEOMEAN values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for sixC. aurispan-resistant isolates was 0.008-0.015 mg/L, and the median and mode MIC values were 0.015 mg/L, demonstrating that MGX retains activity against these isolates. These data support further clinical evaluation of fosmanogepix for the treatment ofC. aurisinfections, including highly resistant isolates.
Development and Characterization of Patient-Derived Xenografts from Non-Small Cell Lung Cancer Brain Metastases
Authors: Baschnagel Andrew M. , Kaushik Saakshi , Durmaz Arda , Goldstein Steve , Ong Irene M. , Abel Lindsey , Clark Paul A. , Leal Ticiana , Buehler Darya , Iyer Gopal , Scott Jacob G. , Kimple Randall J. 
Published: June 2020

AbstractIntroductionThe purpose of this study was to establish and characterize a direct-from patient-derived xenograft (PDX) model of non-small cell lung cancer (NSCLC) brain metastases.MethodsSurgically obtained tissue was implanted subcutaneously and as orthotopic intracranial implants into immunodeficient mice. Histology and DNA loci were compared between original tumor and subsequent PDX passages. Tumors underwent RNA and DNA sequencing and relevant therapeutic targets were identified. Tumor growth rates were assessed following treatment with radiation, MEK inhibitor selumetinib, or MET inhibitor savolitinib. Cell lines were established.ResultsNine NSCLC brain metastases PDXs were established. Morphologically, strong retention of cytoarchitectural features was observed between original patient tumor and subcutaneous and intracranial tumors. Short tandem repeat analysis demonstrated strong concordance between patient tumors and subsequent PDX passages. Transcriptome and mutation analysis revealed high correlation between matched patient and PDX samples. Significant growth inhibition occurred with radiation, with selumetinib in tumors harboring KRAS G12C mutations and with savolitinib in a tumor with MET exon 14 skipping mutation. The combination of radiation and savolitinib resulted in significant tumor growth delay compared to radiation or savolitinib alone our MET exon 14 skipping mutation PDX. Early passage cell strains showed high consistency between patient and PDX tumors.ConclusionWe have established a robust human xenograft model system for investigating NSCLC brain metastases. These PDXs and cell lines show strong phenotypic and molecular correlation with the original patient tumors and provide a valuable resource for testing preclinical therapeutics.
Macrophage-associated lipin-1 transcriptional co-regulatory activity is involved in atherosclerosis
Authors: Blackburn Cassidy M.R. , Schilke Robert M. , Vozenilek Aimee E. , Finck Brian N. , Woolard Matthew D. 
Published: June 2020

AbstractDuring atherosclerosis, macrophages engulf and break down deposited modified low-density lipoproteins (modLDLs) into lipids and free fatty acids. The lipids and free fatty acids from these modLDLs either need to be stored during a process called glycerolipid synthesis or broken down during β-oxidation. In addition, free fatty acids can activate transcription factors to promote a pro-resolving macrophage phenotype. The protein lipin-1 is involved in both glycerolipid synthesis and β-oxidation. Lipin-1 enzymatic activity is a key step in the glycerolipid synthesis pathway; lipin-1 transcriptional co-regulatory activity either augments or represses various transcription factors that are activated via free fatty acids that promote β-oxidation and inhibit inflammation. Lipin-1 enzymatic activity increases pro-inflammatory macrophage phenotypes and is atherogenic. In contrast, we have also demonstrated that lipin-1 transcriptional co-regulatory activity promotes pro-resolving macrophage phenotypes leading us to the hypothesis that lipin-1 transcriptional co-regulatory activity is atheroprotective. Using a mouse model to delete lipin-1 in myeloid cells, we have demonstrated that loss of lipin-1 increases plaque size and pro-inflammatory gene expression. We have also shown mice lacking lipin-1 in myeloid cells have increased plaque collagen deposition and larger necrotic core formation. Combined, these data suggest that though lipin-1 enzymatic activity is atherogenic, lipin-1 transcriptional co-regulatory activity is atheroprotective. Overall, the results suggest that the dual activities of lipin-1 contribute to atherosclerosis progression in opposite ways.
Microfluidics-enabled 96-well perfusion system for high-throughput tissue engineering and long-term all-optical electrophysiology
Authors: Wei Lai , Li Weizhen , Entcheva Emilia , Li Zhenyu 
Published: June 2020

ABSTRACTThis work demonstrates a novel high-throughput (HT) microfluidics-enabled uninterrupted perfusion system (HT-μUPS) and validates its use with chronic all-optical electrophysiology in human excitable cells. HT-μUPS consists of a soft multichannel microfluidic plate cover which could button on a commercial HT 96-well plate. Herein, we demonstrate the manufacturing process of the system and its usages in acute and chronic all-optical electrophysiological studies of human induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CM) and engineered excitable (Spiking HEK) cells. HT-μUPS perfusion maintained functional voltage and calcium responses in iPSC-CM and Spiking HEK cells under spontaneous conditions and under optogenetic pacing. Long-term culture with HT-μUPS improved cell viability and optogenetically-tracked calcium responses in Spiking HEK cells. The scalability and simplicity of this design and its compatibility with HT all-optical electrophysiology can empower cell-based assays for personalized medicine using patient-derived cells.
CaaX-like protease of cyanobacterial origin is required for complex plastid biogenesis in malaria parasites
Authors: Meister Thomas R. , Tang Yong , Pulkoski-Gross Michael J. , Yeh Ellen 
Published: June 2020

AbstractPlasmodiumparasites and related apicomplexans contain an essential “complex plastid” organelle of secondary endosymbiotic origin, the apicoplast. Biogenesis of this complex plastid poses a unique challenge requiring evolution of new cellular machinery. We previously conducted a mutagenesis screen for essential apicoplast biogenesis genes to discover organellar pathways with evolutionary and biomedical significance. Here we validate and characterize a gene candidate from our screen, Pf3D7_0913500. Using a conditional knockdown strain, we show that Pf3D7_0913500 depletion causes growth inhibition that is rescued by the sole essential product of the apicoplast, isopentenyl pyrophosphate (IPP), and results in apicoplast loss. Because Pf3D7_0913500 had no previous functional annotation, we name itapicoplast-minus IPP-rescued 4 (AMR4). AMR4 has an annotated CaaX Protease and Bacteriocin Processing (CPBP) domain, which in eukaryotes typically indicates a role in CaaX post-prenylation processing. Indeed, AMR4 is the only CaaX-like protease inPlasmodiumparasites which are known to require protein prenylation, and we confirm that the conserved catalytic residue of AMR4 is required for its apicoplast function. However, we unexpectedly find that AMR4 does not act in a CaaX post-prenylation processing pathway inP. falciparum. Instead, we find that AMR4 is imported into the apicoplast and is derived from a cyanobacterial CPBP gene which was retained through both primary and secondary endosymbiosis. Our findings suggest that AMR4 is not a true CaaX protease, but instead acts in a conserved, uncharacterized chloroplast pathway that has been retained for complex plastid biogenesis.ImportancePlasmodiumparasites, which cause malaria, and related apicomplexans are important human and veterinary pathogens. These parasites represent a highly divergent and understudied branch of eukaryotes, and as such often defy the expectations set by model organisms. One striking example of unique apicomplexan biology is the apicoplast, an essential but non-photosynthetic plastid derived from an unusual secondary (eukaryote-eukaryote) endosymbiosis. Endosymbioses are a major driver of cellular innovation, and apicoplast biogenesis pathways represent a hotspot for molecular evolution. We previously conducted an unbiased screen for apicoplast biogenesis genes inP. falciparumto uncover these essential and innovative pathways. Here, we validate a novel gene candidate from our screen and show that its role in apicoplast biogenesis does not match its functional annotation predicted by model eukaryotes. Our findings suggest that an uncharacterized chloroplast maintenance pathway has been reused for complex plastid biogenesis in this divergent branch of pathogens.
Behavioural diversity of bonobo prey preference as a potential cultural trait
Authors: Samuni L. , Wegdell F. , Surbeck M. 
Published: June 2020

AbstractThe importance of cultural processes to behavioural diversity, especially in our closest living relatives, is central for revealing the evolutionary origins of human culture. Whereas potential cultural traits are extensively investigated in chimpanzees, our other closest living relative, the bonobo, is often overlooked as a candidate model. Further, a prominent critique to many examples of proposed animal cultures is premature exclusions of environmental confounds known to shape behavioural phenotypes. We addressed these gaps by investigating variation in prey preference expression between neighbouring bonobo groups that associate and share largely overlapping home ranges. We find specific group preference for duiker or anomalure hunting that are otherwise unexplained by variation in spatial usage of hunt locations, seasonality or sizes of hunting parties. Our findings demonstrate that group-specific behaviours emerge independently of the local ecology, indicating that hunting techniques in bonobos may be culturally transmitted. We suggest that the tolerant intergroup relations of bonobos offer an ideal context to explore drivers of behavioural phenotypes, the essential investigations for phylogenetic constructs of the evolutionary origins of culture.
Comparing the electrophysiology and morphology of human and mouse layer 2/3 pyramidal neurons with Bayesian networks
Authors: Mihaljević Bojan , Larrañaga Pedro , Bielza Concha 
Published: June 2020

ABSTRACTPyramidal neurons are the most common neurons in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. We compared human temporal cortex and mouse visual cortex pyramidal neurons from the Allen Cell Types Database in terms of their electrophysiology and basal dendrites’ morphology. We found that, among other differences, human pyramidal neurons had a higher threshold voltage, a lower input resistance, and a larger basal dendritic arbor. We learned Gaussian Bayesian networks from the data in order to identify correlations and conditional independencies between the variables and compare them between the species. We found strong correlations between electrophysiological and morphological variables in both species. One result is that, in human cells, dendritic arbor width had the strongest effect on input resistance after accounting for the remaining variables. Electrophysiological variables were correlated, in both species, even with morphological variables that are not directly related to dendritic arbor size or diameter, such as mean bifurcation angle and mean branch tortuosity. Contrary to previous results, cortical depth was correlated with both electrophysiological and morphological variables, and its effect on electrophysiological could not be explained in terms of the morphological variables. Overall, the correlations among the variables differed strikingly between human and mouse neurons. Besides identifying correlations and conditional independencies, the learned Bayesian networks might be useful for probabilistic reasoning regarding the morphology and electrophysiology of pyramidal neurons.
Neuromotor impairment, hearing loss and blindness in a preclinical mouse model of Charcot Marie-Tooth disorder
Authors: Gonzalez-Gonzalez Sergio , Cazevieille Chantal 
Published: June 2020

AbstractSchwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth (CMT) diseases, that are commonly associated with a process of demyelination. Peripheral neuropathy is a major complication of diabetes, and the pathomechanism of the disease remains poorly studied. Here, we studied the progressive demyelinating process, hearing impairment and blindness observed in the CMT1A mouse model C3. Our results confirm that these mice represent a robust and validated model to study the peripheral neuropathy induced by CMT disorder allowing to determine the efficacy of new pharmacological candidates targeting demyelinating diseases such as CMT1A disorder.