bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial Magnetic Stimulation Over the Human Medial Posterior Parietal Cortex Disrupts Depth Encoding During Reach Planning
Authors: Breveglieri Rossella , Bosco Annalisa , Borgomaneri Sara , Tessari Alessia , Galletti Claudio , Avenanti Alessio , Fattori Patrizia 
Published: July 2020

Abstract
Accumulating evidence supports the view that the medial part of the posterior parietal cortex (mPPC) is involved in the planning of reaching, but while plenty of studies investigated reaching performed toward different directions, only a few studied different depths. Here, we investigated the causal role of mPPC (putatively, human area V6A–hV6A) in encoding depth and direction of reaching. Specifically, we applied single-pulse transcranial magnetic stimulation (TMS) over the left hV6A at different time points while 15 participants were planning immediate, visually guided reaching by using different eye-hand configurations. We found that TMS delivered over hV6A 200 ms after the Go signal affected the encoding of the depth of reaching by decreasing the accuracy of movements toward targets located farther with respect to the gazed position, but only when they were also far from the body. The effectiveness of both retinotopic (farther with respect to the gaze) and spatial position (far from the body) is in agreement with the presence in the monkey V6A of neurons employing either retinotopic, spatial, or mixed reference frames during reach plan. This work provides the first causal evidence of the critical role of hV6A in the planning of visually guided reaching movements in depth.
The Claustrum is Involved in Cognitive Processes Related to the Classical Conditioning of Eyelid Responses in Behaving Rabbits
Authors: Reus-García M Mar , Sánchez-Campusano Raudel , Ledderose Julia , Dogbevia Godwin K , Treviño Mario , Hasan Mazahir T , Gruart Agnès , Delgado-García José M 
Published: July 2020

Abstract
It is assumed that the claustrum (CL) is involved in sensorimotor integration and cognitive processes. We recorded the firing activity of identified CL neurons during classical eyeblink conditioning in rabbits, using a delay paradigm in which a tone was presented as conditioned stimulus (CS), followed by a corneal air puff as unconditioned stimulus (US). Neurons were identified by their activation from motor (MC), cingulate (CC), and medial prefrontal (mPFC) cortices. CL neurons were rarely activated by single stimuli of any modality. In contrast, their firing was significantly modulated during the first sessions of paired CS/US presentations, but not in well-trained animals. Neuron firing rates did not correlate with the kinematics of conditioned responses (CRs). CL local field potentials (LFPs) changed their spectral power across learning and presented well-differentiated CL–mPFC/CL–MC network dynamics, as shown by crossfrequency spectral measurements. CL electrical stimulation did not evoke eyelid responses, even in trained animals. Silencing of synaptic transmission of CL neurons by the vINSIST method delayed the acquisition of CRs but did not affect their presentation rate. The CL plays an important role in the acquisition of associative learning, mostly in relation to the novelty of CS/US association, but not in the expression of CRs.
Multidrug Resistant Tuberculosis With Simultaneously Acquired Drug Resistance to Bedaquiline and Delamanid
Authors: Yoshiyama Takashi , Takaki Akiko , Aono Akio , Mitarai Satoshi , Okumura Masao , Ohta Ken , Kato Seiya 
Published: July 2020

Abstract
This study is the first to report a clinical case of simultaneously acquired resistance to bedaquiline (BDQ) and delamanid (DLM). Whole genome sequencing revealed 2 nucleotide insertions (Rv0678 and fbiC) in the Mycobacterium tuberculosis isolate. The minimum inhibitory concentrations for BDQ and DLM were 0.25 µg/mL and &gt;2.0 µg/mL, respectively.
CYP2B6 Genotype and Weight Gain Differences Between Dolutegravir and Efavirenz
Authors: Griesel Rulan , Maartens Gary , Chirehwa Maxwell , Sokhela Simiso , Akpomiemie Godspower , Moorhouse Michelle , Venter Francois , Sinxadi Phumla 
Published: July 2020

Abstract

Background
Dolutegravir is associated with more weight gain than efavirenz. Loss-of-function polymorphisms in CYP2B6 result in higher efavirenz concentrations, which we hypothesized would impair weight gain among people living with human immunodeficiency virus (HIV; PLWH) starting efavirenz-based antiretroviral therapy (ART).

Methods
We studied ART-naive participants from the ADVANCE study randomized to the efavirenz /emtricitabine/tenofovir disoproxil fumarate (TDF) and dolutegravir/emtricitabine/TDF arms. We compared changes in weight and regional fat on DXA from baseline to week 48 between CYP2B6 metabolizer genotypes in the efavirenz arm, and with the dolutegravir arm.

Results
There were 342 participants in the dolutegravir arm and 168 in the efavirenz arm who consented to genotyping. Baseline characteristics were similar. Weight gain was greater in women than men. In the efavirenz arm CYP2B6 metaboliser genotype was associated with weight gain (P = .009), with extensive metabolizers gaining the most weight, and with changes in regional fat in women, but not in men. Weight gain was similar in CYP2B6 extensive metabolizers in the efavirenz arm and in the dolutegravir arm (P = .836). The following variables were independently associated with weight gain in all participants: baseline CD4 count, baseline human immunodeficiency virus type 1 (HIV-1) RNA, and CYP2B6 metaboliser genotype.

Conclusions
CYP2B6 metaboliser genotype was associated with weight gain in PLWH starting efavirenz-based ART. Weight gain was similar between CYP2B6 extensive metabolizers in the efavirenz arm and in the dolutegravir arm, suggesting that impaired weight gain among CYP2B6 slow or intermediate metabolizers could explain the increased weight gain on dolutegravir compared with efavirenz observed in ADVANCE and other studies.
Evaluation of regenerated tracheal cilia function on a collagen-conjugated scaffold in a canine model
Authors: Ueda Yuichiro , Sato Toshihiko , Nakamura Ryosuke , Tamari Shigeyuki , Muranishi Yusuke , Yutaka Yojiro , Nakamura Tatsuo , Omori Koichi , Iwasaki Akinori , Date Hiroshi 
Published: July 2020

Abstract

OBJECTIVES
It is unclear whether the movement and function of the regenerated cilia on collagen-conjugated artificial trachea are the same as those of normal cilia. This study assessed the ciliary beat frequency (CBF) and ciliary transport functions (CTFs) of regenerated cilia in a canine model.

METHODS
A tracheal defect introduced into the anterior portion of the cervical trachea of an adult beagle dog was covered with a collagen-conjugated prosthesis. Two months later, the trachea was harvested along the long axis, both from normal and regenerated regions. The cilia were stained with isothiocyanate-conjugated wheat germ agglutinin, and their movement was monitored with a high-speed camera to analyse CBF and CTF. Four samples each were obtained from the regenerated and normal regions for CBF analysis and 7 samples each were obtained for CTF analysis.

RESULTS
The wheat germ agglutinin-stained cells showed well-regulated beats in both the regenerated and normal regions of the trachea. Mean CBF in the regenerated and normal regions did not differ significantly (7.11 ± 0.41 vs 7.14 ± 1.09 Hz; P = 981). By contrast, CTF was significantly lower in the regenerated region than in the normal region (30.0 ± 6.62 vs 7.43 ± 0.58 μm/s; P = 0.005).

CONCLUSIONS
Mean CBF in the regenerated and normal regions did not differ significantly at 2 months. The CTF in the regenerated region recovered partially but remained lower than those in the normal region. Methods are needed to improve the CTF of regenerated cilia.
Drug Resistance Mutations and Associated Phenotypes Detected in Clinical Trials of Maribavir for Treatment of Cytomegalovirus Infection
Authors: Chou Sunwen , Song Kening , Wu Jingyang , Bo Tien , Crumpacker Clyde 
Published: July 2020

Abstract

Background
In separate phase 2 trials, 120 patients received maribavir for cytomegalovirus (CMV) infection failing conventional therapy (trial 202) and 119 received maribavir for asymptomatic infection (trial 203). Overall, 172 cleared their CMV infection (CMV DNA &lt;200 copies/mL) within 6 weeks.

Methods
Baseline and posttreatment plasma samples were tested for mutations in viral genes UL97, UL54, and/or UL27. Selected viral mutants were phenotyped for drug susceptibility.

Results
Baseline samples revealed UL54 mutations newly phenotyped as conferring resistance to standard DNA polymerase inhibitor(s), including K493N, P497S, K513T, L565V, V823A, A987V, and E989D. Of 29 patients (including 25 from trial 202) who cleared but later experienced recurrent CMV infection while on maribavir, 23 had available UL97 genotyping data; 17 had known resistance mutations (T409M or H411Y) and 5 additional had UL97 C480F alone. The newly phenotyped mutation C480F conferred high-grade maribavir resistance and low-grade ganciclovir resistance. Among 25 who did not respond to &gt;14 days of therapy, 9 showed T409M or H411Y and 4 others showed C480F alone.

Conclusions
After maribavir therapy (400–1200 mg twice daily), UL97 mutations T409M, H411Y, or C480F emerge to confer maribavir resistance in patients with recurrent CMV infection while on therapy or no response to therapy.

Clinical Trials Registration
NCT01611974 and EudraCT 2010-024247-32.
Progress towards elimination of lymphatic filariasis in the Americas region
Authors: Fontes Gilberto , da Rocha Eliana Maria Mauricio , Scholte Ronaldo Guilherme Carvalho , Nicholls Rubén Santiago 
Published: July 2020

Abstract
In South and Central America, lymphatic filariasis (LF) is caused by Wuchereria bancrofti, which is transmitted by Culex quinquefasciatus, the only vector species in this region. Of the seven countries considered endemic for LF in the Americas in the last decade, Costa Rica, Suriname and Trinidad and Tobago were removed from the World Health Organization list in 2011. The remaining countries, Brazil, Dominican Republic, Guyana and Haiti, have achieved important progress in recent years. Brazil was the first country in the Americas to stop mass drug administration (MDA) and to establish post-MDA surveillance. Dominican Republic stopped MDA in all LF-endemic foci: La Ciénaga and Southwest passed the third Transmission Assessment Survey (TAS) and the Eastern focus passed TAS-1 in 2018. Haiti passed the TAS and interrupted transmission in &gt;80% of endemic communes, achieving effective drug coverage. Guyana implemented effective coverage in MDAs in 2017 and 2018 and in 2019 scaled up the treatment for 100% of the geographical region, introducing ivermectin in the MDA in order to achieve LF elimination by the year 2026. The Americas region is on its way to eliminating LF transmission. However, efforts should be made to improve morbidity management to prevent disability of the already affected populations.
Clinical concept extraction using transformers
Authors: Yang Xi , Bian Jiang , Hogan William R , Wu Yonghui 
Published: July 2020

Abstract

Objective
The goal of this study is to explore transformer-based models (eg, Bidirectional Encoder Representations from Transformers [BERT]) for clinical concept extraction and develop an open-source package with pretrained clinical models to facilitate concept extraction and other downstream natural language processing (NLP) tasks in the medical domain.

Methods
We systematically explored 4 widely used transformer-based architectures, including BERT, RoBERTa, ALBERT, and ELECTRA, for extracting various types of clinical concepts using 3 public datasets from the 2010 and 2012 i2b2 challenges and the 2018 n2c2 challenge. We examined general transformer models pretrained using general English corpora as well as clinical transformer models pretrained using a clinical corpus and compared them with a long short-term memory conditional random fields (LSTM-CRFs) mode as a baseline. Furthermore, we integrated the 4 clinical transformer-based models into an open-source package.

Results and Conclusion
The RoBERTa-MIMIC model achieved state-of-the-art performance on 3 public clinical concept extraction datasets with F1-scores of 0.8994, 0.8053, and 0.8907, respectively. Compared to the baseline LSTM-CRFs model, RoBERTa-MIMIC remarkably improved the F1-score by approximately 4% and 6% on the 2010 and 2012 i2b2 datasets. This study demonstrated the efficiency of transformer-based models for clinical concept extraction. Our methods and systems can be applied to other clinical tasks. The clinical transformer package with 4 pretrained clinical models is publicly available at https://github.com/uf-hobi-informatics-lab/ClinicalTransformerNER. We believe this package will improve current practice on clinical concept extraction and other tasks in the medical domain.
Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy
Authors: Someya Masanori , Tsuchiya Takaaki , Fukushima Yuki , Hasegawa Tomokazu , Takada Yu , Hori Masakazu , Miura Katsutoshi , Kitagawa Mio , Gocho Toshio , Hirohashi Yoshihiko , Torigoe Toshihiko , Iwasaki Masahiro , Matsuura Motoki , Saito Tsuyoshi , Sakata Koh-ichi 
Published: July 2020

Abstract

Objective
To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients.

Methods
We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues.

Results
In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is &lt;70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230.

Conclusion
The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.
Properties of five z ∼ 0.3–0.4 confirmed LyC leakers: VLT/XShooter observations
Authors: Guseva N G , Izotov Y I , Schaerer D , Vílchez J M , Amorín R , Pérez-Montero E , Iglesias-Páramo J , Verhamme A , Kehrig C , Ramambason L 
Published: July 2020

ABSTRACT
Using new Very Large Telescope (VLT)/XShooter spectral observations we analyse the physical properties of five z ∼ 0.3–0.4 confirmed Lyman continuum (LyC) leakers. Strong resonant Mg ii λλ2796, 2803 Å emission lines (I(λλ2796, 2803)/I(Hβ) ≃ 10–38 per cent) and non-resonant Fe ii* λλ2612, 2626 Å emission lines are observed in spectra of five and three galaxies, respectively. We find high electron densities Ne ∼ 400 cm−3, significantly higher than in typical low-z, but comparable to those measured in z ∼ 2–3 star-forming galaxies (SFGs). The galaxies have a mean value of log N/O = –1.16, close to the maximum values found for SFGs in the metallicity range of 12 + log O/H ≃ 7.7–8.1. All 11 low-z LyC emitting galaxies found by Izotov et al., including the ones considered in this study, are characterized by high equivalent width (EW) (Hβ) ∼ 200–400 Å, high ionization parameter (log(U) = –2.5 to –1.7), high average ionizing photon production efficiency ξ = 1025.54 Hz erg−1, and hard ionizing radiation. On the Baldwin–Phillips–Terlevich (BPT) diagram we find the same offset of our leakers from low-z main-sequence SFGs as that for local analogues of Lyman-break galaxies (LBGs) and extreme SFGs at z ∼ 2–3. We confirm the effectiveness of the He i emission lines diagnostics proposed by Izotov et al. in searching for LyC leaker candidates and find that their intensity ratios correspond to those in a median with low neutral hydrogen column density N(H i) = 1017–5 × 1017 cm−2 that permit leakage of LyC radiation, likely due to their density-bounded H ii regions.
The Milky Way’s bulge star formation history as constrained from its bimodal chemical abundance distribution
Authors: Lian Jianhui , Zasowski Gail , Hasselquist Sten , Nataf David M , Thomas Daniel , Moni Bidin Christian , Fernández-Trincado José G , Garcia-Hernandez D A , Lane Richard R , Majewski Steven R , Roman-Lopes Alexandre , Schultheis Mathias 
Published: July 2020

ABSTRACT
We conduct a quantitative analysis of the star formation history (SFH) of the Milky Way’s (MW) bulge by exploiting the constraining power of its stellar [Fe/H] and [Mg/Fe] distribution functions. Using Apache Point Observatory Galactic Evolution Experiment survey data, we confirm the previously established bimodal [Mg/Fe]–[Fe/H] distribution within 3 kpc of the inner Galaxy. To fit the chemical bimodal distribution, we use a simple but flexible star formation framework, which assumes two distinct stages of gas accretion and star formation, and systematically evaluate a wide multidimensional parameter space. We find that the data favour a three-phase SFH that consists of an initial starburst, followed by a rapid star formation quenching episode, and a lengthy, quiescent secular evolution phase. The metal-poor, high-α bulge stars ([Fe/H] &lt; 0.0 and [Mg/Fe] &gt; 0.15) are formed rapidly (&lt;2 Gyr) during the early starburst. The density gap between the high- and low-α sequences is due to the quenching process. The metal-rich, low-α population ([Fe/H] &gt; 0.0 and [Mg/Fe] &lt; 0.15) then accumulates gradually through inefficient star formation during the secular phase. This is qualitatively consistent with the early SFH of the inner disc. Given this scenario, a notable fraction of young stars (age &lt;5 Gyr) is expected to persist in the bulge. Combined with extragalactic observations, these results suggest that a rapid star formation quenching process is responsible for bimodal distributions in both the MW’s stellar populations and in the general galaxy population and thus plays a critical role in galaxy evolution.
All-Cause Mortality and Causes of Death in the Swiss Hepatitis C Cohort Study (SCCS)
Authors: Roelens Maroussia , Bertisch Barbara , Moradpour Darius , Cerny Andreas , Semmo Nasser , Schmid Patrick , Müllhaupt Beat , Clerc Olivier , Semela David , Junker Christoph , Negro Francesco , Keiser Olivia ,   for the Swiss Hepatitis C Cohort Study, Negro Francesco , Kaiser Laurent , Heim Markus , Hirsch Hans , Semmo Nasser , Suter Franziska , Moradpour Darius , Aubert Vincent , Siegrist Hans , Cerny Andreas , Martinetti-Lucchini Gladys , Clerc Olivier , Semela David , Schmid Patrick , Dollenmaier Günter , Müllhaupt Beat , Probst-Müller Elsbeth , Benkert Pascal , Fabbro Thomas , Rutquist Marielle , Sluka Constantin 
Published: July 2020

Abstract

Background
With direct-acting antiviral agents (DAAs), mortality rates and causes of death among persons with hepatitis C virus (HCV) infection may change over time. However, the emergence of such trends may be delayed by the slow progression of chronic hepatitis C. To date, detailed analyses of cause-specific mortality among HCV-infected persons over time remain limited.

Methods
We evaluated changes in causes of death among Swiss Hepatitis C Cohort Study (SCCS) participants from 2008 to 2016. We analyzed risk factors for all-cause and cause-specific mortality, accounting for changes in treatment, fibrosis stage, and use of injectable drugs over time. Mortality ascertainment was completed by linking lost-to-follow-up participants to the Swiss Federal Statistical Office death registry.

Results
We included 4700 SCCS participants, of whom 478 died between 2008 and 2016. The proportion of unknown causes of death decreased substantially after linkage, from 42% to 10%. Leading causes of death were liver failure (crude death rate 4.4/1000 person-years), liver cancer (3.4/1000 person-years), and nonliver cancer (2.8/1000 person-years), with an increasing proportion of cancer-related deaths over time. Cause-specific analysis showed that persons with sustained virologic response were less at risk for liver-related mortality than those never treated or treated unsuccessfully.

Conclusions
Although the expected decrease in mortality is not yet observable, causes of death among HCV-infected persons have evolved over time. With the wider use of DAAs, liver-related mortality is expected to decline in the future. Continued monitoring of cause-specific mortality will remain important to assess the long-term effect of DAAs and design effective interventions.
Collagen Matrix With Mucoperiosteum Graft as an Effective Fatless Flapless Reconstruction After Endoscopic Pituitary Adenoma Resection
Authors: Shahein Mostafa , Montaser Alaa S , Barbero Juan M Revuelta , Maza Guillermo , Todeschini Alexandre B , Otto Bradley A , Carrau Ricardo L , Prevedello Daniel M 
Published: July 2020

Abstract

BACKGROUND
Proper skull base reconstruction after endoscopic endonasal pituitary surgery is of great importance to decrease the rate of complications.

OBJECTIVE
To assess the safety and efficacy of reconstruction with materials other than fat graft and naso-septal flaps (NSF) to avoid their associated morbidities.

METHODS
The authors’ institutional database for patients who underwent endoscopic endonasal approach for pituitary adenoma was reviewed. Exclusion criteria included recurrence, postradiation therapy, and reconstruction by fat graft or NSF. They were divided into group A, where collagen matrix (CM) (DuraGen® Plus Matrix, Integra LifeSciences Corporation, Plainsboro, New Jersey) alone was used; group B, where CM and simple mucoperiosteum graft were used and group C, which included cases without CM utilization.

RESULTS
The study included 252 patients. No age, gender, or body mass index statistically significant difference between groups. Group B included the largest tumor size (23.0 mm) in comparison to groups A (18.0 mm) and C (13.0 mm). Suprasellar extension was more frequently present (49.4%) in comparison to groups A (29.8%, P = .001) and C (21.2%, P < .001). Postoperative cerebrospinal fluid (CSF) leak rate was 0%, 2.9%, and 6% in groups A, B, and C, respectively. In group B, the CSF leak rate decreased from 45.9% intraoperatively to 2.9% postoperatively (P < .001). In group A, the CSF leak reduction rate was almost statistically significant (P = .06).

CONCLUSION
Utilization of CM and simple mucosperiosteal graft in skull base reconstruction following pituitary adenoma surgery is an effective method to avoid the morbidities associated with NSF or fat graft.