bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott–Aldrich syndrome
Authors: Magnani A. , Semeraro M. , Adam F. , Booth C. , Dupré L. , Morris E. C. , Gabrion A. , Roudaut C. , Borgel D. , Toubert A. , Clave E. , Abdo C. , Gorochov G. , Petermann R. , Guiot M. , Miyara M. , Moshous D. , Magrin E. , Denis A. , Suarez F. , Lagresle C. , Roche A. M. , Everett J. , Trinquand A. , Guisset M. , Bayford J. Xu , Hacein-Bey-Abina S. , Kauskot A. , Elfeky R. , Rivat C. , Abbas S. , Gaspar H. B. , Macintyre E. , Picard C. , Bushman F. D. , Galy A. , Fischer A. , Six E. , Thrasher A. J. , Cavazzana M. 
Published: January 2022

AbstractPatients with Wiskott–Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6 years) (phase I/II trial no. NCT02333760) for eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy trials (nos. NCT01347346 and NCT01347242), with a focus on thrombocytopenia and autoimmunity. Primary outcomes of the long-term study were to establish clinical and biological safety, efficacy and tolerability by evaluating the incidence and type of serious adverse events and clinical status and biological parameters including lentiviral genomic integration sites in different cell subpopulations from 3 years to 15 years after gene therapy. Secondary outcomes included monitoring the need for additional treatment and T cell repertoire diversity. An interim analysis shows that the study meets the primary outcome criteria tested given that the gene-corrected cells engrafted stably, and no serious treatment-associated adverse events occurred. Overall, severe infections and eczema resolved. Autoimmune disorders and bleeding episodes were significantly less frequent, despite only partial correction of the platelet compartment. The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.
High-throughput segmentation of unmyelinated axons by deep learning
Authors: Plebani Emanuele , Biscola Natalia P. , Havton Leif A. , Rajwa Bartek , Shemonti Abida Sanjana , Jaffey Deborah , Powley Terry , Keast Janet R. , Lu Kun-Han , Dundar M. Murat 
Published: January 2022

AbstractAxonal characterizations of connectomes in healthy and disease phenotypes are surprisingly incomplete and biased because unmyelinated axons, the most prevalent type of fibers in the nervous system, have largely been ignored as their quantitative assessment quickly becomes unmanageable as the number of axons increases. Herein, we introduce the first prototype of a high-throughput processing pipeline for automated segmentation of unmyelinated fibers. Our team has used transmission electron microscopy images of vagus and pelvic nerves in rats. All unmyelinated axons in these images are individually annotated and used as labeled data to train and validate a deep instance segmentation network. We investigate the effect of different training strategies on the overall segmentation accuracy of the network. We extensively validate the segmentation algorithm as a stand-alone segmentation tool as well as in an expert-in-the-loop hybrid segmentation setting with preliminary, albeit remarkably encouraging results. Our algorithm achieves an instance-level $$F_1$$

F
1

score of between 0.7 and 0.9 on various test images in the stand-alone mode and reduces expert annotation labor by 80% in the hybrid setting. We hope that this new high-throughput segmentation pipeline will enable quick and accurate characterization of unmyelinated fibers at scale and become instrumental in significantly advancing our understanding of connectomes in both the peripheral and the central nervous systems.
Extracting microplastic decay rates from field data
Authors: Metz T. , Koch M. , Lenz P. 
Published: January 2022

AbstractBeing able to estimate and predict future microplastic distributions in the environment is one of the major challenges of the rapidly developing field of microplastic research. However, this task can only be achieved if our understanding of the decay of individual microplastic particles is significantly enhanced. Here, we show by using a rate equation model that currently available data of size distributions measured at single times cannot provide useful insights into this process. To analyze what data contains more information we generated more complex artificial data mimicking subsequent measurements using a stochastic simulation algorithm. Applying our model to this data revealed the following minimal requirements for future experimental data: (1) data should be collected as time series at identical spots and (2) size measurements should be combined with mass measurements. In contrast to currently available data, flux rates and decay parameters of individual particles can be extracted from such data.
Revealing the effect of seed phosphorus concentration on seedling vigour and growth of rice using mutagenesis approach
Authors: Yugandhar Poli , Veronica Nallamothu , Subrahmanyam D. , Brajendra P. , Nagalakshmi S. , Srivastava Akanksha , Voleti S. R. , Sarla N. , Sundaram R. M. , Sevanthi Amitha Mithra , Singh A. K. , Mangrauthia Satendra K. 
Published: January 2022

AbstractThe harvested plant products, specifically, the grains of cereals are major drivers of soil phosphorus (P) depletion. However, the breeding or biotechnology efforts to develop low P seeds have not been attempted because of possible adverse effects on seedling vigour and crop establishment. Several studies have contradictory observations on influence of seed P on seedling vigour. Lack of appropriate genetic material has been the major bottleneck in reaching the consensus. In this study, we used 30 EMS induced mutants of rice cultivar Nagina22 to understand the role of seed P on seedling vigour and associated physiological processes. Seedling vigour, morpho-physiological characteristics, acid phosphatases, alpha-amylase, and expression of P transporter genes were analyzed in seedlings obtained from seeds of high and low grain P mutants. The study suggests that seed P has a significant role on seedling vigour, chlorophyll content and photosynthesis process of young seedlings, and P transport from roots. Notably, we identified few mutants such as NH4791, NH4785, NH4714, NH4663, NH4614, and NH4618 which showed least influence of low seed P on seedling vigour and other metabolic processes. Therefore, these mutants can be used in breeding programs aiming for development of low P grains. Also, these and other identified mutants can be used to decipher the genetic and molecular mechanisms regulating the differential response of seed P on germination, seedling vigour and several other physiological processes influencing the crop growth and establishment.
The application of a deep learning system developed to reduce the time for RT-PCR in COVID-19 detection
Authors: Lee Yoonje , Kim Yu-Seop , Lee Da-in , Jeong Seri , Kang Gu-Hyun , Jang Yong Soo , Kim Wonhee , Choi Hyun Young , Kim Jae Guk , Choi Sang-hoon 
Published: January 2022

AbstractReducing the time to diagnose COVID-19 helps to manage insufficient isolation-bed resources and adequately accommodate critically ill patients. There is currently no alternative method to real-time reverse transcriptase polymerase chain reaction (RT-PCR), which requires 40 cycles to diagnose COVID-19. We propose a deep learning (DL) model to improve the speed of COVID-19 RT-PCR diagnosis. We developed and tested a DL model using the long short-term memory method with a dataset of fluorescence values measured in each cycle of 5810 RT-PCR tests. Among the DL models developed here, the diagnostic performance of the 21st model showed an area under the receiver operating characteristic (AUROC), sensitivity, and specificity of 84.55%, 93.33%, and 75.72%, respectively. The diagnostic performance of the 24th model showed an AUROC, sensitivity, and specificity of 91.27%, 90.00%, and 92.54%, respectively.
Near-infrared photoluminescence of Portland cement
Authors: Meng Wei , Bachilo Sergei M. , Parol Jafarali , Nagarajaiah Satish , Weisman R. Bruce 
Published: January 2022

AbstractPortland cement emits bright near-infrared photoluminescence that can be excited by light wavelengths ranging from at least 500–1000 nm. The emission has a peak wavelength near 1140 nm and a width of approximately 30 nm. Its source is suggested to be small particles of silicon associated with calcium silicate phases. The luminescence peak wavelength appears independent of the cement hydration state, aggregates, and mechanical strain but increases weakly with increasing temperature. It varies slightly with the type of cement, suggesting a new non-contact method for identifying cement formulations. After a thin opaque coating is applied to a cement or concrete surface, subsequent formation of microcracks exposes the substrate’s near-infrared emission, revealing the fracture locations, pattern, and progression. This damage would escape detection in normal imaging inspections. Near-infrared luminescence imaging may therefore provide a new tool for non-destructive testing of cement-based structures.
Impact of hemolysis on multi-OMIC pancreatic biomarker discovery to derisk biomarker development in precision medicine studies
Authors: Searfoss Richard , Shah Punit , Ofori-Mensa Kennedy , Bussberg Valerie , Tolstikov Vladimir , Greenwood Bennett , Li Hongyan , Richardson Kris , Miller Gregory M. , DeCicco Corinne , Granger Elder , Rodrigues Leonardo O. , Grund Eric M. , Moser A. James , Sarangarajan Rangaprasad , Narain Niven R. , Kiebish Michael A. 
Published: January 2022

AbstractCancer biomarker discovery is critically dependent on the integrity of biofluid and tissue samples acquired from study participants. Multi-omic profiling of candidate protein, lipid, and metabolite biomarkers is confounded by timing and fasting status of sample collection, participant demographics and treatment exposures of the study population. Contamination by hemoglobin, whether caused by hemolysis during sample preparation or underlying red cell fragility, contributes 0–10 g/L of extraneous protein to plasma, serum, and Buffy coat samples and may interfere with biomarker detection and validation. We analyzed 617 plasma, 701 serum, and 657 buffy coat samples from a 7-year longitudinal multi-omic biomarker discovery program evaluating 400+ participants with or at risk for pancreatic cancer, known as Project Survival. Hemolysis was undetectable in 93.1% of plasma and 95.0% of serum samples, whereas only 37.1% of buffy coat samples were free of contamination by hemoglobin. Regression analysis of multi-omic data demonstrated a statistically significant correlation between hemoglobin concentration and the resulting pattern of analyte detection and concentration. Although hemolysis had the greatest impact on identification and quantitation of the proteome, distinct differentials in metabolomics and lipidomics were also observed and correlated with severity. We conclude that quality control is vital to accurate detection of informative molecular differentials using OMIC technologies and that caution must be exercised to minimize the impact of hemolysis as a factor driving false discovery in large cancer biomarker studies.
The composition of the fluid phase in inclusions in synthetic HPHT diamonds grown in system Fe–Ni–Ti–C
Authors: Sonin Valeri , Tomilenko Anatoly , Zhimulev Egor , Bul’bak Taras , Chepurov Aleksei , Babich Yuri , Logvinova Alla , Timina Tat’yana , Chepurov Anatoly 
Published: January 2022

AbstractDiamonds grown by high pressure high temperature process (HPHT) are usually characterized by yellow color and high contents of nitrogen. Introduction of Ti decreases nitrogen content in diamond. Understanding the formation of nitrogen-poor diamond is very important not for the progress of HPHT process only, but because these diamond varieties represent the rare natural stones, although their crystallization conditions have not been clarified yet. Here we studied the composition of fluid phase in synthetic diamonds. The experiments were performed using a high-pressure apparatus BARS at pressures 5.5–6.0 GPa and temperatures 1350–1400 °C. It was found that introduction of metallic Ti leads to concentration of nitrogen mainly as nitrogenated hydrocarbons. The hypothesis that elucidates the formation of low-nitrogen diamond in Fe–Ni is proposed: the presence of Ti leads to an increase of hydrogen fugacity in the metal melt which drastically reduces the nitrogen solubility. As a result, nitrogen concentrates in the form of complex hydrocarbon compounds, while diamond grows colorless and characterized by very low nitrogen content. It is suggested that the proposed mechanism acts the same way in the presence of other metals which are strong reducing agents.
Travertine crystal growth ripples record the hydraulic history of ancient Rome’s Anio Novus aqueduct
Authors: Keenan-Jones Duncan , Motta Davide , Garcia Marcelo H. , Sivaguru Mayandi , Perillo Mauricio , Shosted Ryan K. , Fouke Bruce W. 
Published: January 2022

AbstractTravertine crystal growth ripples are used to reconstruct the early hydraulic history of the Anio Novus aqueduct of ancient Rome. These crystalline morphologies deposited within the aqueduct channel record the hydraulic history of gravity-driven turbulent flow at the time of Roman operation. The wavelength, amplitude, and steepness of these travertine crystal growth ripples indicate that large-scale sustained aqueduct flows scaled directly with the thickness of the aqueous viscous sublayer. Resulting critical shear Reynolds numbers are comparable with those reconstructed from heat/mass transfer crystalline ripples formed in other natural and engineered environments. This includes sediment transport in rivers, lakes, and oceans, chemical precipitation and dissolution in caves, and melting and freezing in ice. Where flow depth and perimeter could be reconstructed from the distribution and stratigraphy of the travertine within the Anio Novus aqueduct, flow velocity and rate have been quantified by deriving roughness-flow relationships that are independent of water temperature. More generally, under conditions of near-constant water temperature and kinematic viscosity within the Anio Novus aqueduct channel, the travertine crystal growth ripple wavelengths increased with decreasing flow velocity, indicating that systematic changes took place in flow rate during travertine deposition. This study establishes that travertine crystal growth ripples such as those preserved in the Anio Novus provide a sensitive record of past hydraulic conditions, which can be similarly reconstructed from travertine deposited in other ancient water conveyance and storage systems around the world.
Transplantation of 3D adipose-derived stem cell/hepatocyte spheroids alleviates chronic hepatic damage in a rat model of thioacetamide-induced liver cirrhosis
Authors: Wu Yu Chiuan , Wu Guan Xuan , Chen Kuan Wei , Shiu Li-Yen , Kumar Satheesh , Liu Guei-Sheung , Kuo Shyh Ming 
Published: January 2022

AbstractCirrhosis refers to irreversible liver damage where healthy tissue is replaced by scar tissue, resulting in impaired liver function. There is no cure and current treatments only prevent further liver damage; thus, novel therapeutic options are urgently needed. Here, we report a new approach that enables the formation of self-assembled 3D spheroids of adipose-derived stem cells (ADSCs) and murine hepatocytes (AML12) via reconstituted collagen fibers. Compared with the spheroids formed in the commercially available EZSHERE dish, the collagen fiber-based ADSC/hepatocyte spheroids offer a notable benefit in structure formation and paracrine factor secretion. To test the regenerative capability of the collagen fiber-based 3D ADSC/hepatocyte spheroids, a rat model of thioacetamide (TAA)-induced liver cirrhosis was employed. The transplantation of the collagen fiber-based 3D ADSC/hepatocyte spheroids show an improvement in liver function and ameliorates pathological liver cirrhosis in TAA-treated rats. In summary, our data show collagen fiber-based self-assembled 3D ADSC/hepatocyte spheroids to possess the excellent regenerative capacity in response to TAA-induced liver injury, promising an alternative therapeutic strategy for liver cirrhosis.
Association between aesthetic satisfaction and chronic postsurgical pain in breast cancer patients treated with one stage prosthesis implantation
Authors: Wang Baona , Gao Peng , Wang Jing , Zheng Hui 
Published: January 2022

AbstractThis study retrospectively studied the incidence of chronic post-surgical pain (CPSP) following single-stage implant-based breast reconstruction (IBBR) and evaluated the possible risk factors. This was a retrospective cohort study, involving all patients undergoing single-stage IBBR between January and December 2019. The follow-up was completed between January and March 2021. The scores for satisfaction (SS) were based on the BREAST-Q, while the pain burden index (PBI) was used to assess the degree of CPSP. The questionnaires were completed by 159 patients. CPSP occurred in 48.43% of the patients, 2.52% of them being severe cases. Significant predictors for the development of CPSP in the univariate analysis included severe acute postoperative pain (PP), a history of preoperative chronic pain, psychological disorders, SS with the reconstructed breasts, and whether there were any regrets about having had the reconstruction. Multivariate analysis identified severe acute PP (odds ratio (OR) = 2.80, 95% confidence interval (CI) = 1.16–6.79, p = 0.023), a history of preoperative chronic pain (OR = 3.39, 95% CI = 1.42–8.10, p = 0.006), and the SS (OR = 0.86, 95% CI = 0.75–0.99, p = 0.034) as being independently associated with the development of CPSP. In subgroup analysis, the PBI of the patients in the SS < 12 group (p < 0.001), the bilateral group (p < 0.01), and the severe acute PP group (p < 0.005) was significantly higher than the PBI of those in the control groups. This study demonstrated a significant incidence of CPSP following single-stage IBBR, and the patients with lower SS of their reconstructed breasts developed more CPSP. Lower SS, bilateral procedures, and severe acute PP were predictors of higher PBI.Trial registration: Registered in Chictr.org.cn registry system on 24 February 2020 (ChiCTR2000030139).
Combined MEK/MDM2 inhibition demonstrates antitumor efficacy in TP53 wild-type thyroid and colorectal cancers with MAPK alterations
Authors: Pairawan Seyed , Akcakanat Argun , Kopetz Scott , Tapia Coya , Zheng Xiaofeng , Chen Huiqin , Ha Min Jin , Rizvi Yasmeen , Holla Vijaykumar , Wang Jing , Evans Kurt W. , Zhao Ming , Busaidy Naifa , Fang Bingliang , Roth Jack A. , Dumbrava Ecaterina Ileana , Meric-Bernstam Funda 
Published: January 2022

AbstractMost tumors with activating MAPK (mitogen-activated protein kinase) pathway alterations respond poorly to MEK inhibitors alone. Here, we evaluated combination therapy with MEK inhibitor selumetinib and MDM2 inhibitor KRT-232 in TP53 wild-type and MAPK altered colon and thyroid cancer models. In vitro, we showed synergy between selumetinib and KRT-232 on cell proliferation and colony formation assays. Immunoblotting confirmed p53 upregulation and MEK pathway inhibition. The combination was tested in vivo in seven patient-derived xenograft (PDX) models (five colorectal carcinoma and two papillary thyroid carcinoma models) with different KRAS, BRAF, and NRAS mutations. Combination therapy significantly prolonged event-free survival compared with monotherapy in six of seven models tested. Reverse-phase protein arrays and immunohistochemistry, respectively, demonstrated upregulation of the p53 pathway and in two models cleaved caspase 3 with combination therapy. In summary, combined inhibition of MEK and MDM2 upregulated p53 expression, inhibited MAPK signaling and demonstrated greater antitumor efficacy than single drug therapy in both in vitro and in vivo settings. These findings support further clinical testing of the MEK/MDM2 inhibitor combination in tumors of epithelial origin with MAPK pathway alterations.
Association of anemia and iron parameters with mortality among prevalent peritoneal dialysis patients in Taiwan: the AIM-PD study
Authors: Kuo Ko-Lin , Liu Jia-Sin , Lin Ming-Huang , Hsu Chih-Cheng , Tarng Der-Cherng ,   the Taiwan Society of Nephrology Renal Registry Data System Research Group, Hung Szu-Chun , Kuo Ko-Lin , Liu Jia-Sin , Hsu Chih-Cheng , Lin Ming-Huang , Tarng Der-Cherng , Tseng Wei-Cheng , Tsai Ming-Tsun , Ou Shuo-Ming , Yang Chih-Yu , Lin Yao-Ping , Lin Yi-Sheng , Wu Chia-Lin , Hung Tung-Po 
Published: January 2022

AbstractIn 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10–11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.
Cross-border malaria in the triple border region between Brazil, Venezuela and Guyana
Authors: Abdallah Rispah , Louzada Jaime , Carlson Christina , Ljolje Dragan , Udhayakumar Venkatachalam , Oliveira-Ferreira Joseli , Lucchi Naomi W. 
Published: January 2022

AbstractThe state of Roraima, in Brazil, has recently seen an increase in the number of reported Plasmodium falciparum infections believed to be imported from neighboring countries. The objective of this study was to determine the prevalence of Plasmodium species among patients attending malaria health posts in Roraima and quantify the infections attributable to imported malaria. This cross-sectional case study was carried out between March 2016 and September 2018. Study participants were recruited as they exited the malaria health post. Information about residence, occupation and travel history was collected using a questionnaire. A dried blood spot was collected and used for malaria diagnosis by PCR. A total of 1222 patients were enrolled. Of the 80% Plasmodium positive samples, 50% were P. falciparum, 34% P. vivax, 8% mixed P. falciparum/P. vivax and 0.2% mixed P. falciparum/P. ovale infections and 8% tested positive for Plasmodium, but the species could not be identified. 80% of the malaria patients likely acquired infections in Venezuela and the remaining 20% acquired in Guyana, Brazil, Suriname and French Guyana. 50% of the study participants reported to be working in a mine. Results from this study support the hypothesis that imported malaria contribute to the bulk of malaria diagnosed in Roraima. These findings are in keeping with previous findings and should be considered when developing malaria control interventions.