bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent TMS-EEG to reveal the neuroplastic changes in the prefrontal and insular cortices in the analgesic effects of DLPFC-rTMS
Authors: Ye Yang , Wang Jinghua , Che Xianwei 
Published: December 2021

Abstract
The dorsolateral prefrontal cortex (DLPFC) is an important target for repetitive transcranial magnetic stimulation (rTMS) to reduce pain. However, the analgesic efficacy of DLPFC-rTMS needs to be optimized, in which the mechanisms of action remain unclear. Concurrent TMS and electroencephalogram (TMS-EEG) is able to evaluate neuroplastic changes beyond the motor cortex. Using TMS-EEG, this study was designed to investigate the local and distributed neuroplastic changes associated with DLPFC analgesia. Thirty-four healthy adults received DLPFC or sham stimulation in a randomized, crossover design. In each session, participants underwent cold pain and TMS-EEG assessment both before and after 10-Hz rTMS. We provide novel findings that DLPFC analgesia is associated with a smaller N120 amplitude in the contralateral prefrontal cortex as well as with a larger N120 peak in the ipsilateral insular cortex. Furthermore, there was a strong negative correlation between N120 changes of these two regions whereby the amplitude changes of this dyad were associated with increased pain threshold. In addition, DLPFC stimulation enhanced coherence between the prefrontal and somatosensory cortices oscillating in the gamma frequency. Overall, our data present novel evidence on local and distributed neuroplastic changes associated with DLPFC analgesia.
Ledipasvir/Sofosbuvir for Patients Coinfected With Chronic Hepatitis C and Hepatitis B in Taiwan: Follow-up at 108 Weeks Posttreatment
Authors: Liu Chun Jen , Sheen I Shyan , Chen Chi Yi , Chuang Wan Long , Wang Horng Yuan , Tseng Kuo Chih , Chang Ting Tsung , Yang Jenny , Massetto Benedetta , Suri Vithika , Camus Gregory , Jiang Deyuan , Zhang Fangqiu , Gaggar Anuj , Hu Tsung Hui , Hsu Yu Chun , Lo Gin Ho , Chu Chi Jen , Chen Jyh Jou , Peng Cheng Yuan , Chien Rong Nan , Chen Pei Jer 
Published: December 2021

Abstract

Background
For patients coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to HBV reactivation. We evaluated HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up.

Methods
In Taiwan, 111 patients with HCV genotype 1 or 2 and HBV received ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks. HBV virologic reactivation was defined as postbaseline increase in HBV DNA from either less than the lower limit of quantification (LLOQ, 20 IU/mL) to equal to or more than LLOQ or equal to or more than LLOQ to &gt;1 log10 IU/mL. HBV clinical reactivation was HBV virologic reactivation with alanine aminotransferase (ALT) &gt;2× upper limit of normal. Factors associated with development of HBV virologic or clinical reactivation were evaluated with logistic regression analysis.

Results
All patients (100%, 111/111) maintained HCV suppression through 108 weeks after treatment. HBV virologic reactivation occurred in 73% of patients (81/111). Clinical reactivation occurred in 9% (10/111). The majority of HBV virologic reactivations (86%, 70/81) occurred by follow-up week 12, whereas clinical reactivation was generally more delayed. Eight (7%, 8/111) initiated HBV therapy. In regression analyses, baseline HBV DNA and hepatitis B surface antigen (HBsAg) levels were associated with HBV virologic reactivation and baseline ALT and HBV DNA, and HBsAg levels were associated with HBV clinical reactivation.

Conclusion
Among HCV/HBV coinfected patients treated with direct-acting antivirals for HCV, HBV virologic reactivation occurred in a majority of patients during treatment and follow-up. In most patients, HBV virologic reactivation was asymptomatic; only a small proportion initiated HBV treatment. Notably, clinical reactivation may still occur &gt;3 months after end of therapy.

Clinical Trials Registration
NCT02613871.
Duration of Severe Acute Respiratory Syndrome Coronavirus 2 Natural Immunity and Protection Against the Delta Variant: A Retrospective Cohort Study
Authors: Kim Priscilla , Gordon Steven M , Sheehan Megan M , Rothberg Michael B 
Published: December 2021

Abstract

Background
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be highly protective against reinfection and symptomatic disease. However, effectiveness against the Delta variant and duration of natural immunity remain unknown.

Methods
This retrospective cohort study included 325 157 patients tested for SARS-CoV-2 via polymerase chain reaction (PCR) from 9 March 2020 to 31 December 2020 (Delta variant analysis) and 152 656 patients tested from 9 March 2020 to 30 August 2020 (long-term effectiveness analysis) with subsequent testing through 9 September 2021. The primary outcome was reinfection, defined as a positive PCR test &gt;90 days after the initial positive test.

Results
Among 325 157 patients tested before 31 December 2020, 50 327 (15.5%) tested positive. After 1 July 2021 (Delta dominant period), 40 (0.08%) initially positive and 1494 (0.5%) initially negative patients tested positive. Protection of prior infection against reinfection with Delta was 85.4% (95% confidence interval [CI], 80.0–89.3). For the long-term effectiveness analysis, among 152 656 patients tested before 30 August 2020, 11 186 (7.3%) tested positive. After at least 90 days, 81 (0.7%) initially positive and 7167 (5.1%) initially negative patients tested positive. Overall protection of previous infection was 85.7% (95% CI, 82.2–88.5) and lasted up to 13 months. Patients aged &gt;65 years had slightly lower protection.

Conclusions
SARS-CoV-2 infection is highly protective against reinfection with Delta. Immunity from prior infection lasts at least 13 months. Countries facing vaccine shortages should consider delaying vaccinations for previously infected patients to increase access.
How to remove an embolized TriClip from the femoral vein? A case report
Authors: Ajmi Issameddine , Schnupp Steffen , Mady Hesham , Mahnkopf Christian 
Published: December 2021

Abstract

Background and case summary
We report a case of a 76-year-old female who was admitted to our hospital because of dyspnoea caused by a known high-grade tricuspid valve regurgitation (TR). The patient received an edge-to-edge reparation of the tricuspid valve 1 month before the current admission using the TriClip XTR (Clip) system. The post-interventional echocardiographic results were satisfying, and the patient was discharged with TR grade I. At this new admission, the echocardiographic control showed a missing Clip on the tricuspid valve with a recurrent high-grade regurgitation. Fluoroscopy showed the dislocated Clip at the level of the femoral vein. This was also confirmed using Duplex sonography with no signs of thrombosis or embolization. The challenge was how to extract the Clip using endovascular methods as the patient refused any kind of surgical removal. We managed to remove the 20 × 10 mm big clip using transfemoral access and an endovascular snare system. No post-interventional complications were registered. The patient was discharged after the intervention with a new scheduled Clip procedure.

Discussion
This case shows a possible safe and challenging alternative to removing dislocated Clip from the femoral vein. Experienced operators are required to have the knowledge and skills to manage these possible procedural complications using the appropriate apparatus. A surgical technique would be, in this case, common practice, however as the patient declined surgical intervention, the endovascular approach was the alternative option.
‘Superimposed miracles’: an extremely rare case of a septuagenarian with an unrepaired tetralogy of Fallot: a case report
Authors: Suzuki Makiko , Matsumoto Kensuke , Izawa Yu , Hirata Ken-Ichi 
Published: December 2021

Abstract

Background
Although the life expectancy of patients with tetralogy of Fallot (TOF) is comparable to that of the general population due to advancements in surgical intervention, if untreated, patients with TOF may die during their childhood. However, it has been anecdotally reported that a small number of patients with unrepaired TOF survived into their senescence.

Case summary
A 71-year-old man with a history of multiple heart failure admissions was referred to our institute after successful cardiopulmonary arrest resuscitation. Transthoracic echocardiography showed the overriding of the aorta on a large ventricular septal defect and right ventricular hypertrophy, along with severe pulmonary stenosis (PS), all of which indicated unrepaired TOF. Computed tomography revealed a patent Blalock–Taussig shunt, which was constructed at the age of 19 years. Coronary angiography revealed multivessel coronary stenoses. Although radical intracardiac repair was not performed due to his multiple comorbidities, his heart failure symptoms were significantly improved owing to proper medication titration. One year following discharge, the patient was well and enjoyed playing golf.

Discussion
Specific anatomical, functional, and haemodynamic characteristics may be required for the long-term survival of patients with TOF. Pulmonary stenosis should be initially mild to guarantee pulmonary flow during childhood and adolescence, and gradual PS exacerbation should be paralleled with systemic-to-pulmonary collateral development or an extracardiac shunt. Moreover, reduced left ventricular compliance may act as a balancing factor against a right-to-left shunt. The presence of all of these special requirements may have contributed to the unusual survival for this patient.
Gastrin: From Physiology to Gastrointestinal Malignancies
Authors: Duan Suzann , Rico Karen , Merchant Juanita L 
Published: December 2021

Abstract
Abetted by widespread usage of acid-suppressing proton pump inhibitors (PPIs), the mitogenic actions of the peptide hormone gastrin are being revisited as a recurring theme in various gastrointestinal (GI) malignancies. While pathological gastrin levels are intricately linked to hyperplasia of enterochromaffin-like cells leading to carcinoid development, the signaling effects exerted by gastrin on distinct cell types of the gastric mucosa are more nuanced. Indeed, mounting evidence suggests dichotomous roles for gastrin in both promoting and suppressing tumorigenesis. Here, we review the major upstream mediators of gastrin gene regulation, including inflammation secondary to Helicobacter pylori infection and the use of PPIs. We further explore the molecular biology of gastrin in GI malignancies, with particular emphasis on the regulation of gastrin in neuroendocrine neoplasms. Finally, we highlight tissue-specific transcriptional targets as an avenue for targetable therapeutics.
Adaptive Evolution in TRIF Leads to Discordance between Human and Mouse Innate Immune Signaling
Authors: Hyland Edel M , Webb Andrew E , Kennedy Kathy F , Gerek Ince Z Nevin , Loscher Christine E , O’Connell Mary J 
Published: December 2021

Abstract
The TIR domain-containing adapter inducing IFN-β (TRIF) protein is an innate immune system protein that mediates the MyD88-independent toll-like receptor response pathway in mice and humans. Previously, we identified positive selection at seven distinct residues in mouse TRIF (mTRIF), as compared with human and other mammalian orthologs, thus predicting protein functional shift in mTRIF. We reconstructed TRIF for the most recent common ancestor of mouse and human, and mutated this at the seven sites to their extant mouse/human states. We overexpressed these TRIF mutants in immortalized human and mouse cell lines and monitored TRIF-dependent cytokine production and gene expression induction. We show that optimal TRIF function in human and mouse is dependent on the identity of the positively selected sites. These data provide us with molecular data relating observed differences in response between mouse and human MyD88-independent signaling in the innate immune system with protein functional change.
A role for the Erk MAPK pathway in modulating SAX-7/L1CAM-dependent locomotion inCaenorhabditis elegans
Authors: Moseley-Alldredge Melinda , Sheoran Seema , Yoo Hayoung , O’Keefe Calvin , Richmond Janet E , Chen Lihsia 
Published: December 2021

AbstractL1CAMs are immunoglobulin cell adhesion molecules that function in nervous system development and function. Besides being associated with autism and schizophrenia spectrum disorders, impaired L1CAM function also underlies the X-linked L1 syndrome, which encompasses a group of neurological conditions, including spastic paraplegia and congenital hydrocephalus. Studies on vertebrate and invertebrate L1CAMs established conserved roles that include axon guidance, dendrite morphogenesis, synapse development, and maintenance of neural architecture. We previously identified a genetic interaction between the Caenorhabditis elegans L1CAM encoded by the sax-7 gene and RAB-3, a GTPase that functions in synaptic neurotransmission; rab-3; sax-7 mutant animals exhibit synthetic locomotion abnormalities and neuronal dysfunction. Here, we show that this synergism also occurs when loss of SAX-7 is combined with mutants of other genes encoding key players of the synaptic vesicle (SV) cycle. In contrast, sax-7 does not interact with genes that function in synaptogenesis. These findings suggest a postdevelopmental role for sax-7 in the regulation of synaptic activity. To assess this possibility, we conducted electrophysiological recordings and ultrastructural analyses at neuromuscular junctions; these analyses did not reveal obvious synaptic abnormalities. Lastly, based on a forward genetic screen for suppressors of the rab-3; sax-7 synthetic phenotypes, we determined that mutants in the ERK Mitogen-activated Protein Kinase (MAPK) pathway can suppress the rab-3; sax-7 locomotion defects. Moreover, we established that Erk signaling acts in a subset of cholinergic neurons in the head to promote coordinated locomotion. In combination, these results suggest a modulatory role for Erk MAPK in L1CAM-dependent locomotion in C. elegans.
An extracellular matrix damage sensor signals through membrane-associated kinase DRL-1 to mediate cytoprotective responses inCaenorhabditis elegans
Authors: Wimberly Keon , Choe Keith P 
Published: December 2021

AbstractWe and others previously identified circumferential bands of collagen named annular furrows as key components of a damage sensor in the cuticle of Caenorhabditis elegans that regulates cytoprotective genes. Mutation or loss of noncollagen secreted proteins OSM-7, OSM-8, and OSM-11 activate the same cytoprotective responses without obvious changes to the cuticle indicating that other extracellular proteins are involved. Here, we used RNAi screening to identify protein kinase DRL-1 as a key modulator of cytoprotective gene expression and stress resistance in furrow and extracellular OSM protein mutants. DRL-1 functions downstream from furrow disruption and is expressed in cells that induce cytoprotective genes. DRL-1 is not required for the expression of cytoprotective genes under basal or oxidative stress conditions consistent with specificity to extracellular signals. DRL-1 was previously shown to regulate longevity via a “Dietary Restriction-Like” state, but it functions downstream from furrow disruption by a distinct mechanism. The kinase domain of DRL-1 is related to mammalian MEKK3, and MEKK3 is recruited to a plasma membrane osmosensor complex by a scaffold protein. In C. elegans, DRL-1 contains an atypical hydrophobic C-terminus with predicted transmembrane domains and is constitutively expressed at or near the plasma membrane where it could function to receive extracellular damage signals for cells that mount cytoprotective responses.
Refining slip distribution in moderate earthquakes using Sentinel-1 burst overlap interferometry: a case study over 2020 May 15Mw 6.5 Monte Cristo Range Earthquake
Authors: Cui Yan , Ma Zhangfeng , Aoki Yosuke , Liu Jihong , Yue Dongjie , Hu Jia , Zhou Cheng , Li Zhen 
Published: December 2021

SUMMARYAzimuth and range measurements from Synthetic Aperture Radar (SAR) images are commonly used to depict the coseismic deformation of large earthquakes. Azimuth measurements associated with moderate-sized earthquakes are hardly applicable due to their limited accuracy. In this paper, we first explored the capability of Sentinel-1 azimuth measurements to map the coseismic deformation of a moderate earthquake. We used both range and azimuth offset measurements to map the coseismic deformation of the 2020 Mw 6.5 Monte Cristo Range earthquake in Nevada. Optimal dip angles of the two main faults and the slip model were obtained. By adding azimuth displacements as constraints, the inverted slip model reveals shallower and more refined slip than models only constrained by InSAR and GPS data, highlighting the importance of introducing the azimuth measurements to the moderate earthquake. The preferred fault model shows a mixture of left-lateral and normal faulting on the western segment and a left-lateral slip on the eastern segment. We found that the inferred faults might verify the clockwise rotation block model, which has been proposed to accommodate fault slip across the Mina deflection. Moreover, a shallow alluvial basin and the young left-lateral fault within the left bend can potentially be responsible for the orientation and normal slip components in the western fault segment, respectively.
Pharmacokinetics, Pharmacodynamics, and Safety of Etrolizumab in Children With Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease: Results from a Phase 1 Randomized Trial
Authors: Zhang Wenhui , Scalori Astrid , Fuh Franklin , McBride Jacqueline , She Gaohong , Kierkus Jaroslaw , Korczowksi Bartosz , Li Regan , Abouhossein Mariam , Kadva Alysha , Park K T , Tang Meina Tao 
Published: December 2021

Abstract

Background
Etrolizumab, a humanized anti-β7 antibody, has not been studied in children. Here, we evaluate the pharmacokinetics, pharmacodynamics, and safety of etrolizumab in children with inflammatory bowel disease.

Methods
Patients age 4 to 17 years with moderately to severely active ulcerative colitis or Crohn’s disease were randomized 1:1 to receive 1.5mg/kg of etrolizumab subcutaneously every 4 weeks (q4w) or 3.0mg/kg every 8 weeks (q8w) for 16 weeks in this open-label phase 1 trial. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed.

Results
Of the 24 patients treated, 21 completed the study. In the groups of 1.5mg/kg q4w and 3.0mg/kg q8w, respectively, mean (SD) maximum concentration (Cmax) was 9.8 (4.86) µg/mL and 18.1 (6.25) µg/mL; and mean (SD) area under the curve within a dosing interval (AUCtau) was 167 (86.9) and 521 (306) μg·day/mL after the last dose. The Cmax increased dose proportionally. The AUC over an 8-week period was slightly higher in the 3.0mg/kg q8w dose group. Median half-life was similar for both dosing regimens. Median numbers of free β7high gut-homing T and B cell subsets declined below 10% of baseline, confirming β7 target engagement and complete/near-complete receptor occupancy. Adverse events were consistent with the safety profile in adults. Approximately 60% of patients achieved a clinical response.

Conclusions
Etrolizumab showed a dose-proportional increase in Cmax and a slightly greater than dose-proportional increase in AUCtau. Both regimens achieved complete/near-complete β7 receptor occupancy, with a similar relationship to concentration as adults. Etrolizumab was well tolerated and demonstrated clinical activity in children.
Dermal Denticle Diversity in Sharks: Novel Patterns on the Interbranchial Skin
Authors: Gabler-Smith Molly K , Wainwright Dylan K , Wong Greta A , Lauder George V 
Published: December 2021

Synopsis
Shark skin is covered in dermal denticles—tooth-like structures consisting of enameloid, dentine, and a central pulp cavity. Previous studies have demonstrated differences in denticle morphology both among species and across different body regions within a species, including one report of extreme morphological variation within a 1 cm distance on the skin covering the branchial pouches, a region termed “interbranchial skin.” We used gel-based profilometry, histology, and scanning electron microscopy to quantify differences in denticle morphology and surface topography of interbranchial skin denticles among 13 species of sharks to better understand the surface structure of this region. We show that (1) interbranchial skin denticles differ across shark species, and (2) denticles on the leading edge of the skin covering each gill pouch have different morphology and surface topography compared with denticles on the trailing edge. Across all species studied, there were significant differences in denticle length (P = 0.01) and width (P = 0.002), with shorter and wider leading edge denticles compared with trailing edge denticles. Surface skew was also higher in leading edge denticles (P = 0.009), though most values were still negative, indicating a surface texture more dominated by valleys than peaks. Overall, leading edge denticles were smoother-edged than trailing edge denticles in all of the species studied. These data suggest two hypotheses: (1) smoother-edged leading edge denticles protect the previous gill flap from abrasion during respiration, and (2) ridged denticle morphology at the trailing edge might alter water turbulence exiting branchial pouches after passing over the gills. Future studies will focus on determining the relationship between denticle morphology and water flow by visualizing fluid motion over interbranchial denticles during in vivo respiration.
Automation of mass vaccination against COVID-19 at an academic health center
Authors: Suarez Maritza , Botwinick Avi , Akkiraju Ravi , Pebanco Gilbert , Franceschi Dido , Ruiz Jose , Reis David , Weiss Roy E 
Published: December 2021

Abstract
As vaccines against COVID-19 became available for distribution, the University of Miami addressed several challenges to facilitate vaccine allocation to the highest risk employees, patients, and students. Advanced use of technology allowed for the automation of key processes in the mass vaccination effort, which expedited vaccine outreach and scheduling, while maintaining routine delivery of healthcare services. The University’s employees were initially prioritized for vaccination; employees who opted in were stratified into 5 vaccine administration phases. A similar process was implemented for students. When the state of Florida mandated expansion of vaccine allocation to include individuals aged 65 and older, an algorithm for patients was designed, taking into account age, comorbidities, date of last visit, and presence of an activated patient portal account. Innovative use of technology allowed for 19  000 vaccines to be administered within the first 37 days, which comprised 100% vaccine allotment, without wasting a single vaccine dose.