bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome and genome evolution during HER2-amplified breast neoplasia
Authors: Lu Peipei , Foley Joseph , Zhu Chunfang , McNamara Katherine , Sirinukunwattana Korsuk , Vennam Sujay , Varma Sushama , Fehri Hamid , Srivastava Arunima , Zhu Shirley , Rittscher Jens , Mallick Parag , Curtis Christina , West Robert 
Published: July 2021

Abstract
Background
The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia’s fitness is less understood.

Methods
Here we use spatially oriented genomic approaches to identify transcriptomic and genetic changes at the single-duct level within precursor neoplasia associated with invasive breast cancer. We study HER2 amplification in ductal carcinoma in situ (DCIS) as an event that can be both quantified and spatially located via fluorescence in situ hybridization (FISH) and immunohistochemistry on fixed paraffin-embedded tissue.

Results
By combining the HER2-FISH with the laser capture microdissection (LCM) Smart-3SEQ method, we found that HER2 amplification in DCIS alters the transcriptomic profiles and increases diversity of copy number variations (CNVs). Particularly, interferon signaling pathway is activated by HER2 amplification in DCIS, which may provide a prolonged interferon signaling activation in HER2-positive breast cancer. Multiple subclones of HER2-amplified DCIS with distinct CNV profiles are observed, suggesting that multiple events occurred for the acquisition of HER2 amplification. Notably, DCIS acquires key transcriptomic changes and CNV events prior to HER2 amplification, suggesting that pre-amplified DCIS may create a cellular state primed to gain HER2 amplification for growth advantage.

Conclusion
By using genomic methods that are spatially oriented, this study identifies several features that appear to generate insights into neoplastic progression in precancer lesions at a single-duct level.
An individual randomised efficacy trial of autologous blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in leprosy in Nepal: the TABLE trial protocol
Authors: Napit Indra B. , Shrestha Dilip , Bishop Jon , Choudhury Sopna , Dulal Santosh , Gill Paramjit , Gkini Eleni , Gwyther Holly , Hagge Deanna A. , Neupane Karuna , Sartori Jo , Slinn Gemma , Watson Samuel I. , Lilford Richard 
Published: July 2021

Abstract
Background
Leprosy is curable with multidrug therapy and treatment in the early stages can prevent disability. However, local nerve damage can lead to injury and consequently recurring and disfiguring ulcers. The aim of this study is to evaluate the treatment of leprosy ulcers using an autologous blood product; leukocyte and platelet-rich fibrin (L-PRF) to promote healing.

Methods
This is a single-centre study in the Anandaban Hospital, The Leprosy Mission Nepal, Kathmandu, Nepal. Consenting patients (n=130) will be individually randomised in a single-blinded, controlled trial. Participants will be 18 years of age or older, admitted to the hospital with a clean, dry and infection-free chronic foot ulcer between 2 and 20 cm2 in size. If the ulcer is infected, it will be treated before enrolment into the study. The intervention involves the application of leukocyte and platelet-rich fibrin (L-PRF) matrix on the ulcer beds during twice-weekly dressing changes. Controls receive usual care in the form of saline dressings only during their twice-weekly dressing changes. Primary outcomes are the rate of healing assessed using standardised photographs by observers blind to allocated treatment, and time to complete re-epithelialization. Follow-up is at 6 months from randomisation.

Discussion
This research will provide valuable information on the clinical and cost-effectiveness of L-PRF in the treatment of leprosy ulcers. An additional benefit is the evaluation of the effects of treatment on quality of life for people living with leprosy ulcers. The results will improve our understanding of the scalability of this treatment across low-income countries for ulcer healing in leprosy and potentially other conditions such as diabetic ulcers.

Trial registration
ISRCTN14933421. Registered on 16 June 2020
Charged aerosol detector response modeling for fatty acids based on experimental settings and molecular features: a machine learning approach
Authors: Pawellek Ruben , Krmar Jovana , Leistner Adrian , Djajić Nevena , Otašević Biljana , Protić Ana , Holzgrabe Ulrike 
Published: July 2021

AbstractThe charged aerosol detector (CAD) is the latest representative of aerosol-based detectors that generate a response independent of the analytes’ chemical structure. This study was aimed at accurately predicting the CAD response of homologous fatty acids under varying experimental conditions. Fatty acids from C12 to C18 were used as model substances due to semivolatile characterics that caused non-uniform CAD behaviour. Considering both experimental conditions and molecular descriptors, a mixed quantitative structure–property relationship (QSPR) modeling was performed using Gradient Boosted Trees (GBT). The ensemble of 10 decisions trees (learning rate set at 0.55, the maximal depth set at 5, and the sample rate set at 1.0) was able to explain approximately 99% (Q2: 0.987, RMSE: 0.051) of the observed variance in CAD responses. Validation using an external test compound confirmed the high predictive ability of the model established (R2: 0.990, RMSEP: 0.050). With respect to the intrinsic attribute selection strategy, GBT used almost all independent variables during model building. Finally, it attributed the highest importance to the power function value, the flow rate of the mobile phase, evaporation temperature, the content of the organic solvent in the mobile phase and the molecular descriptors such as molecular weight (MW), Radial Distribution Function—080/weighted by mass (RDF080m) and average coefficient of the last eigenvector from distance/detour matrix (Ve2_D/Dt). The identification of the factors most relevant to the CAD responsiveness has contributed to a better understanding of the underlying mechanisms of signal generation. An increased CAD response that was obtained for acetone as organic modifier demonstrated its potential to replace the more expensive and environmentally harmful acetonitrile.
A case–control study on the association of intestinal flora with ulcerative colitis
Authors: Tang Yin-hua , Liu Hong-cheng , Song Guang , Wu Tian-tian , Zhao Ying , Shi Li-jun 
Published: July 2021

AbstractThe association between intestinal flora and ulcerative colitis (UC) was studied in order to provide a basis and method for clinical treatment. Fresh fecal samples were collected from 30 active UC patients and 10 healthy controls. The intestinal flora DNA from each sample was extracted and 16S rRNA gene sequencing was carried out using HiSeq platform to identify the intestinal flora in fecal samples. The richness and diversity of intestinal flora in UC patients were significantly lower than those in healthy control group (P < 0.05). Significant differences were observed between the intestinal flora-species of UC patients and healthy controls. Synergistetes (P < 0.01) and Firmicutes (P < 0.05), along with probiotics Veillonella (P < 0.01), Ruminococcus and Coprococcus (P < 0.05) in the UC patients were lower than that in the healthy controls significantly. Furthermore, compared with the control group, Tenericutes (P < 0.01) and intestinal pathogenic bacteria, including Bacteroides (P < 0.01), Escherichia and Sutterella (P < 0.05) were significantly increased. The incidence of UC is significantly associated with the changes in intestinal flora. Changes in intestinal flora may lead to a decrease in the diversity of intestinal flora or to the enrichment of a particular intestinal flora.
Maternal supplementation with phytogenic additives influenced the faecal microbiota and reproductive potential in sows
Authors: Nowland Tanya L. , Stanley Dragana , Kirkwood Roy N. , Torok Valeria A. , Bajagai Yadav S. , Gannon Neil J. , Plush Kate J. 
Published: July 2021

AbstractSows undergo physiological stress during gestation and lactation, potentially leading to enteric dysbiosis and reduced reproductive potential. Phytogenic additives (PFs) may improve performance via their antioxidant, anti-inflammatory and antimicrobial properties. This study determined whether the provision of a gestation/lactation diet containing PAs would alter the gastrointestinal microbiota of sows and their piglets, and improve performance. Sows received a commercial diet throughout gestation and lactation (CTR; n = 64), a commercial diet throughout gestation and a diet containing PAs in lactation (CTR-PA; n = 63) or a commercial diet containing PAs in gestation and lactation (PA; n = 90). Sows were weighed and backfat recorded after mating and at entry and exit from the farrowing house and piglets were weighed on days 1 and 21 of life. Faecal samples collected from sows at farrowing house entry and piglets at 21 and 35 d were subjected to 16 S rRNA gene amplicon analysis. The addition of PAs to sow diets resulted in more piglets born (P = 0.03), however, it did not improve the number of liveborn piglets (P = 0.14). There were no differences in sow weight, P2 backfat depth or lactation feed intake observed. PAs had no effect on piglet weight or survival to weaning but did alter the faecal microbiota of sows, and this change was observed in piglets at 21 and 35 d. PA supplementation to sows has the potential to increase litter size, while also potentially influencing gastrointestinal tract health of the sow and piglets reared.
Pathological alterations in the gastrointestinal tract of a porcine model of DMD
Authors: Zou Xiaodong , Ouyang Hongsheng , Pang Daxin , Han Renzhi , Tang Xiaochun 
Published: July 2021

Abstract
Background
Patients with Duchenne muscular dystrophy (DMD) develop severe skeletal and cardiac muscle pathologies, which result in premature death. Therefore, the current therapeutic efforts are mainly targeted to correct dystrophin expression in skeletal muscle and heart. However, it was reported that DMD patients may also exhibit gastrointestinal and nutritional problems. How the pathological alterations in gastrointestinal tissues contribute to the disease are not fully explored.

Results
Here we employed the CRISPR/Cas9 system combined with somatic nuclear transfer technology (SCNT) to establish a porcine model of DMD and explored their pathological alterations. We found that genetic disruption of dystrophin expression led to morphological gastrointestinal tract alterations, weakened the gastrointestinal tract digestion and absorption capacity, and eventually led to malnutrition and gastric dysfunction in the DMD pigs.

Conclusions
This work provides important insights into the pathogenesis of DMD and highlights the need to consider the gastrointestinal dysfunction as an additional therapeutic target for DMD patients.
National and regional trends in MRI utilization in the face of the ongoing COVID-19 pandemic
Authors: Luxenburg Osnat , Saban Mor , Myers Vicki , Vaknin Sharona , Boldor Noga , Wilf-Miron Rachel 
Published: July 2021

Abstract
Background and purpose
Marked reductions in imaging exams have been documented during the COVID-19 pandemic. The study aimed to examine the effect of the two waves of COVID-19 on magnetic resonance imaging (MRI) utilization at the national and regional level.

Materials and methods
A retrospective-archive study was conducted in Israel, comparing March–December 2020 with March–December 2018 and 2019. Data on MRI utilization were obtained from the national MRI registry, while data on confirmed COVID-19 cases, by place of residence, were obtained from the Israeli Ministry of Health open COVID-19 database.

Results
The number and rate of MRI examinations decreased during the first COVID-19 wave, with the steepest drop in April 2020: 47.5% relative decrease compared to April 2019, and 42.2% compared to 2018. This was followed by a compensatory increase between the waves and a return to almost pre-pandemic levels of use, with just a modest decrease, during the second, more intense COVID wave, compared with the previous year. Existing differences between regions increased during the pandemic. The rate ratio of MRI exams between Tel-Aviv and the Northern periphery increased from 2.89 in April 2019 to 3.94 in April 2020. Jerusalem metropolitan region, with the largest burden of COVID disease, demonstrated only a modest decrease (1%) in MRI utilization during the first 10 months of the pandemic.

Conclusions
At the national level, time trends in reduced MRI utilization followed the first wave of COVID-19, and were accompanied by increased regional disparities. These changes were not explained by differences in the burden of COVID-19 disease but might be explained by unequal distribution of MRI scanners among regions. Reduced utilization was not evident during the second wave, nor at the beginning of the third wave, despite higher COVID-19 case load, demonstrating adaptation to the new normal. Patterns of MRI utilization might help policy-makers and healthcare managers predict the behavior of imaging as well as other sectors, such as elective surgical procedures, during an ongoing pandemic. This forecast might help to manage the lasting effects of the pandemic, including extended waiting times, in the months and years following its remission. In preparation for future national emergencies, timely and detailed data on MRI utilization can serve as a “sensor” for a wide array of diagnostic and interventional medical activities, providing policy-makers with an updated snapshot to guide their response at the regional and national levels.
Leveraging discrete modulation and liquid metal antennas for interference reduction
Authors: Baig Mirza Uzair , Elassy Kareem S. , Høst-Madsen Anders , Ohta Aaron T. , Shiroma Wayne A. , Nosratinia Aria 
Published: July 2021

AbstractRecent progress in the understanding of the behavior of the interference channel has led to valuable insights: first, discrete signaling has been discovered to have tangible benefits in the presence of interference,
especially when one does not wish to decode the interfering signal, i.e., the interference is treated as noise, and second, the capacity of the interference channel as a function of the interference link gains is now understood to be highly irregular, i.e., non-monotonic and discontinuous. This work addresses these two issues in an integrated and interdisciplinary manner: it utilizes discrete signaling to approach the capacity of the interference channel by developing lower bounds on the mutual information under discrete modulation and treating interference as noise, subject to an outage set, and addresses the issue of sensitivity to link gains with a liquid metal reconfigurable antenna to avoid the aforementioned outage sets. Simulations illustrate the effectiveness of our approach.
New coincidence point results for generalized graph-preserving multivalued mappings with applications
Authors: Hammad Hasanen A. , De la Sen Manuel , Agarwal Praveen 
Published: July 2021

AbstractThis research aims to investigate a novel coincidence point (cp) of generalized multivalued contraction (gmc) mapping involved a directed graph in b-metric spaces (b-ms). An example and some corollaries are derived to strengthen our main theoretical results. We end the manuscript with two important applications, one of them is interested in finding a solution to the system of nonlinear integral equations (nie) and the other one relies on the existence of a solution to fractional integral equations (fie).
COVID-19 vaccination associated severe immune thrombocytopenia
Authors: Shah Syed Raza Ali , Dolkar Sherpa , Mathew Jacob , Vishnu Prakash 
Published: July 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has emerged as a deadliest global pandemic after its identification in December 2019 in Wuhan, China resulting in more than three million deaths worldwide. Recently FDA issued emergency authorization for three vaccines for prevention of COVID-19. Here in, we report three cases of severe immune thrombocytopenia (ITP) following COVID-19 vaccination and their clinical course.

Case presentations
Case #1: 53 year old male with past medical history of Crohn’s disease was admitted for myalgias and diffuse petechial rash 8 days after receiving second dose of Pfizer-BioNTech COVID-19 vaccine. A complete blood test showed a platelet count of 2 × 109/L. Patient did not have a prior history of thrombocytopenia and other causes of thrombocytopenia were ruled out by history and pertinent lab data. He received two doses of intravenous immunoglobulin and oral dexamethasone for 4 days resulting in normalization of platelet counts.
Case #2: 67 year male with past medical history of chronic ITP in remission was admitted for melena 2 days after receiving his first dose of Pfizer-BioNTech COVID-19 vaccine. A complete blood test showed a platelet count of 2 × 109/L. Physical exam showed generalized petechiae. There was no history of recent flares of ITP and patient had normal platelet counts following his splenectomy 4 years ago. He received two doses of IVIG and oral dexamethasone for 4 days with gradual improvement in platelet counts.
Case #3: 59 year old female with past medical history of chronic ITP secondary to SLE was admitted for bloody diarrhea 2 days after receiving her first dose of Johnson and Johnson COVID-19 vaccine. Physical exam was unremarkable. A complete blood test showed platelet count of 64 × 109/L which dropped to 27 × 109/L during hospital course. She received oral dexamethasone for 4 days with improvement in platelet counts.

Conclusion
COVID-19 vaccination induced ITP has been recently acknowledged. However, given very few cases and limited data, currently there are no guidelines for management of ITP caused by COVID-19 vaccine as well as vaccination of people with predisposing conditions.
Simultaneous degradation of two mycotoxins enabled by a fusion enzyme in food-grade recombinant Kluyveromyces lactis
Authors: Xia Yu , Wu Zifeng , He Rui , Gao Yahui , Qiu Yangyu , Cheng Qianqian , Ma Xiaoyuan , Wang Zhouping 
Published: July 2021

AbstractAflatoxin B1 (AFB1) and zearalenone (ZEN) are two predominant mycotoxins ubiquitously found in corn, peanuts, and other grains, which pose a great threat to human health. Therefore, safe and effective methods for detoxification of these mycotoxins are urgently needed. To achieve simultaneous degradation of multiple mycotoxins, a fusion enzyme ZPF1 was constructed by linking zearalenone hydrolase and manganese peroxidase with a linker peptide GGGGS. This fusion enzyme was secretory expressed successfully in the newly constructed food-grade recombinant strain Kluyveromyces lactis GG799(pKLAC1-ZPF1), and was investigated with the mycotoxins degradation efficiency in two reaction systems. Results showed that both AFB1 and ZEN can be degraded by ZPF1 in reaction system 1 (70.0 mmol/L malonic buffer with 1.0 mmol/L MnSO4, 0.1 mmol/L H2O2, 5.0 µg/mL AFB1 and ZEN, respectively) with the ratios of 46.46% and 38.76%, respectively. In reaction system 2 (50.0 mmol/L Tris–HCl, with 5.0 µg/mL AFB1 and ZEN, respectively), AFB1 cannot be degraded while ZEN can be degraded with the ratio of 35.38%. To improve the degradation efficiency of these mycotoxins, optimization of the induction and degradation conditions were fulfilled subsequently. The degradation ratios of AFB1 and ZEN by ZPF1 in reaction system 1 reached 64.11% ± 2.93% and 46.21% ± 3.17%, respectively. While in reaction system 2, ZEN was degraded by ZPF1 at a ratio of 41.45% ± 3.34%. The increases of degradation ratios for AFB1 and ZEN in reaction system 1 were 17.65% and 7.45%, respectively, while that for ZEN in reaction system 2 was 6.07%, compared with the unoptimized results.
Rare occurrence of severe blindness and deafness in Friedreich ataxia: a case report
Authors: Damásio Joana , Sardoeira Ana , Araújo Maria , Carvalho Isabel , Sequeiros Jorge , Barros José 
Published: July 2021

Abstract
Background
Friedreich ataxia is the most frequent hereditary ataxia worldwide. Subclinical visual and auditory involvement has been recognized in these patients, with co-occurrence of severe blindness and deafness being rare.

Case report
We describe a patient, homozygous for a 873 GAA expansion in the FXN gene, whose first symptoms appeared by the age of 8. At 22 years-old he developed sensorineural deafness, and at 26 visual impairment. Deafness had a progressive course over 11 years, until a stage of extreme severity which hindered communication. Visual acuity had a catastrophic deterioration, with blindness 3 years after visual impairment was first noticed. Audiograms documented progressive sensorineural deafness, most striking for low frequencies. Visual evoked potentials disclosed bilaterally increased P100 latency. He passed away at the age of 41 years old, at a stage of extreme disability, blind and deaf, in addition to the complete phenotype of a patient with Friedreich ataxia of more than 30 years duration.

Discussion
Severe vision loss and extreme deafness has been described in very few patients with Friedreich ataxia. Long duration, severe disease and large expanded alleles may account for such an extreme phenotype; nonetheless, the role of factors as modifying genes warrants further investigation in this subset of patients.
A totally extraperitoneal approach for endoscopic resection of a congenital prepubic sinus through the pubic symphysis
Authors: Fukuhara Masahiro , Onishi Shun , Yonemura Yusuke , Sato Tomoe , Tsutsumi Satoshi , Bandoh Toshio , Utsunomiya Tohru , Esumi Genshiro 
Published: July 2021

Abstract
Background
A congenital prepubic sinus (CPS) is a rare congenital anomaly in which a duct remnant extends from the skin opening near the pubic symphysis to various parts and the lesions are mostly located in the preperitoneal space. The totally extraperitoneal (TEP) approach is an operational method that provides a good field of view for the preperitoneal space. We report the CPS through the pubic symphysis in which complete resection was achieved by a TEP approach. TEP approach was minimally invasive and achieved satisfactory cosmetic outcome.

Case presentation
We herein report the case of a 13-year-old boy with a fistula opening near the dorsal penis. He was admitted to our hospital due to fever and lower abdominal pain. Abdominal ultrasonography and computed tomography revealed an abscess inside a fistula lumen on the posterior surface of the rectus abdominis muscles in the midline of the lower abdomen. Under a diagnosis of CPS, which was located in the preperitoneal space, endoscopic resection was performed by a totally extraperitoneal approach. After making an umbilical incision, the rectus abdominis muscle was excised outward to expose the preperitoneal space. A single-port system was placed in the preperitoneal space. Three 5-mm-port trocars were inserted. As the preperitoneal cavity was expanded, a sinus connecting to the pubic symphysis was confirmed. The pubic symphysis did not connect with the bladder. Because the fistula was penetrated with the pubic symphysis, the remaining caudal fistula was removed from the body surface with a small spindle-shaped incision around the fistula opening. Finally, the sinus was completely resected, with confirmation from both the cranial side and dorsal side of the pubic symphysis. We were able to perform complete resection of the CPS with good visibility and without any peritoneal damage. There were no intraoperative complications. His postoperative course was uneventful during the 1-year follow-up.

Conclusions
The TEP approach may be feasible for the resection of a CPS and may allow safe and secure resection due to good visibility, even in pediatric patients.