bluuebunny/crossref_metadata_2025 huggingface dataset:
O45 OUTCOMES OF INCISIONAL HERNIA REPAIR SURGERY AFTER MULTIPLE RE-RECURRENCES: A PROPENSITY SCORE MATCHED ANALYSIS
Authors: Sneiders Dimitri , Smet Gijs de , Hartog Floris den , Yurtkap Yagmur , Menon Anand , Jeekel Johannes , Kleinrensink Gert-Jan , Lange Johan , Gillion Jean-François
Published: December 2021

Aim

Patients with a re-recurrent hernia may account for up to 20% of all incisional hernia (IH) patients. IH repair in this population may be complex due to an altered anatomical and biological situation as a result of previous procedures and outcomes of IH repair in this population have not been thoroughly assessed. This study aims to assess outcomes of IH repair by dedicated hernia surgeons in patients who have already had two or more re-recurrences.

Material and Methods

A propensity score matched analysis was performed using a registry-based, prospective cohort. Patients who underwent IH repair after ≥ 2 re-recurrences operated between 2011 and 2018 and who fulfilled 1 year follow-up visit were included. Patients with similar follow-up who underwent primary IH repair were propensity score matched (1:3) and served as control group. Patient baseline characteristics, surgical and functional outcomes were analyzed and compared between both groups.

Results

Seventy-three patients operated on after ≥ 2 IH re-recurrences were matched to 219 patients undergoing primary IH repair. After propensity score matching, no significant differences in patient baseline characteristics were present between groups. The incidence of re-recurrence was similar between groups (≥ 2 re-recurrences: 25% versus control 24%, p = 0.811). The incidence of complications, as well as long-term pain, was similar between both groups.

Conclusions

IH repair in patients who have experienced multiple re-recurrences results in outcomes comparable to patients operated for a primary IH with a similar risk profile. Further surgery in patients who have already experienced multiple hernia re-recurrences is justifiable when performed by a dedicated hernia surgeon.
O51 BIOSYNTHETIC MESH VERSUS NON-ABSORBABLE SYNTHETIC MESH IN COMPLEX ABDOMINAL WALL REPAIR (CAWR): A UK NHS COST-CONSEQUENCE ANALYSIS OF MANAGEMENT STRATEGIES
Authors: Daniels Ian , O'Neill Frank , Martin Antony , Inman Nick , Slater Kellee
Published: December 2021

Aim

CAWR is marked by high complication and hernia recurrence rates. Different management strategies of CAWR may result in a significant reduction in quality of life and increased financial burden. The use of certain non-absorbable synthetic meshes in CAWR may be associated with an increased risk of adverse events for certain patients. Recent evidence suggests that biosynthetic meshes may contribute to lower complications and may be more cost-effective.

Material and Methods

To compare the cost between a synthetic mesh, and a bio-synthetic mesh in the management of patients undergoing CAWR. A cost-consequence model was developed to simulate clinical pathways for patients undergoing CAWR with different management strategies. Clinical parameters were informed by literature review and expert opinion. Adverse events associated with the use of a mesh, resource utilisation and re-admissions were compared between patient management strategies over a period of two years. Costing information were gathered from national tariffs using NICE methodology.

Results

Use of a biosynthetic mesh was associated with a significant reduction in total costs (£15,489 / €17,953) compared to a synthetic mesh at two years. Cost-savings were driven by a lower rate adverse events (hernia recurrence [2% vs.8%] and sepsis [5% vs. 12%] respectively), and resource utilisation after the initial procedure in the management of complications. There was no difference in the intra-procedural time and complications.

Conclusions

The use of a certain biosynthetic mesh is likely to be highly cost saving compared to a certain synthetic mesh in high-risk patients undergoing CAWR. Well conducted comparative clinical studies are needed to inform robust economic modelling.
OV05 CONCOMITANT MIRS (MINI INVASIVE RIVES STOPPA) AND DREAM (DIASTASIS REPAIR ENDOSCOPICALLY ASSISTED MINI-INVASIVE) FOR THE CORRECTION OF COMBINED VENTRAL HERNIA AND DIASTASIS RECTI
Authors: Ngo Philipppe , Cossa Jean Pierre , Pelissier Edouard
Published: December 2021

Aim

Concomitant MIRS (Minimally Invasive Rives-Stoppa) and DREAM (Diastasis Repair Endoscopically Assisted Minimally-invasive) for the correction of combined ventral hernias and diastasis recti.

Material and Methods

The video shows the combined repair of umbilical hernia and diastasis correction by concomitant minimally invasive hernia repair without division of the posterior sheath and diastasis correction by parietoscopy.

Results

A short periumbilical incision is performed, the Alexis retractor is put in place, preaponeurotic dissection is carried out by direct access and two axial incisions of both anterior sheaths are performed parallel to and 1cm next to the midline.

The umbilical hernia and one unexpected epigastric hernia are reduced and repaired by suture. Additional suture approximating the medial borders of anterior sheath incisions over the previous suture is performed to strengthen the repair.

The patch is deployed in the retromuscular space superficial to the suture line, without any incision of the posterior sheath and without any fixation.

Then the top of the Alexis retractor and the camera are put in place, insufflation at 10mm Hg is started and the parietoscopic step is carried out. Two 5mm trocars are placed and preaponeurotic dissection is extended up to the xiphoid process. The diastasis correction is carried out by a continuous suture approximating both rectus muscles from the xiphoid process to the umbilical hernia suture.

Conclusions

The MIRS technique consists of retromuscular patch repair without division of the posterior sheath, and concomitant DREAM technique reinforces the hernia repair and provides diastasis correction.
OV15 EMERGENCY SURGERY OF OBSTRUCTED VENTRAL HERNIA USING TAPP TECHNIQUE: A SAFE AND FEASIBLE APPROACH
Authors: Vaello Victor , Santana Angela , Oto Diego , Juez Luz , Arranz Raquel , Porrero Belen , Molina Jose Manuel , Hernando Luis Blázquez
Published: December 2021

Aim

to explain and show the feasibility of laparoscopic TAPP technique in emergency procedures

Material and Methods

we present a 71-year-old female with personal history of obesity (BMI 32) and a laparoscopic right hemicolectomy performed in 2018, presenting at the ER with a 24-hour intestinal obstruction due to incarcerated ventral incisional hernia.

Results

laparoscopic reduction of the hernia contents was achieved without need of intestinal resection, prior to access to the preperitoneal space, creating a peritoneal flap that was dissected around the hernia. Following closure of the hernia defect, a polypropylene mesh was placed and the peritoneal flap closed. There were no intraoperative or postoperative events and patient was discharged on 3rd POD.

Conclusions

laparoscopic approach to emergency hernias in selected patients doesn’t differ from elective surgery, and offers great advantages in terms of evaluation of the incarcerated elements, and postoperative recovery, especially in obese patients where a conventional open approach has higher morbidity.
OV16 MASSIVE COMPLEX INGUINAL HERNIA
Authors: Elhage Sharbel , Otero Javier , Watson Michael , Davis Bradley , Todd Heniford B
Published: December 2021

Aim

Massive complex inguinal hernias can be exceptionally difficult to repair, especially when they are associated with loss of domain (LOD). We aim to demonstrate an open preperitoneal approach to a complex massive inguinal hernia extending into the scrotum with severe LOD.

Material and Methods

Footage from clinic, diagnostic imaging, and all operative procedures was included. This included botulinum toxin A (BTA) injection, diagnostic laparoscopy and placement of a peritoneal catheter, outpatient pre-operative progressive pneumoperitoneum (PPP), and the preperitoneal hernia repair.

Results

A 53-year-old male construction worker with a known inguinal hernia presented with worsening groin and scrotal pain, associated with fever. CT imaging showed an abscess secondary to perforated diverticulitis within his massive inguinal hernia, as well as massive loss of domain with almost all small and large intestine within the hernia. He was treated with antibiotics and percutaneous drainage in preparation for surgery. He received pre-operative bilateral BTA injection in the oblique abdominal musculature. Subsequently, he underwent diagnostic laparoscopy and peritoneal catheter placement. He received 2 weeks of outpatient PPP. He then underwent open inguinal hernia repair with left orchiectomy and total abdominal colectomy. The hernia was repaired with a biologic mesh placed in the pre-peritoneal plane. The patient recovered very well and had no wound complications post-operatively. He has since followed up in clinic multiple times with no recurrence and excellent cosmetic results.

Conclusions

In this patient with a complex massive inguinal hernia and loss of domain, we demonstrate a successful open preperitoneal repair following pre-operative BTA injection and PPP.
OV17 LAPAROSCOPIC REPAIR OF A DIAPHRAGMATIC EVENTRATION
Authors: Maillo Carmen , Abreu Raquel Camacho , Piçarra Genoveva , Oliveira Maria de Jesús , Figueiredo Nuno
Published: December 2021

Aim

Diaphragmatic eventration (DE) is a rare condition affecting 0,05% of general population. DE is the abnormal elevation of a portion of a entire hemidiaphragm due to a lack of muscle or nerve function. It can be congenital or acquired. The most common cause of DE is cardiac surgery. It can be asymptomatic or present mild symptoms as dispnea, palpitations, pneumonia.

Material and Methods

61 years old male with medical history of arterial hypertension, DMII, Hyperlipidemia.

He had a motor vehicle accident with 6 to 9 left ribs fractures.

One month later complained of dyspnea with shortness of air to normal activity. Rx: elevation of left diaphragm. CT scan: elevation of left diaphragm without rupture, passive atelectasis of inferior left lobe of the lung.

He initiated respiratory physiotherapy without improvement of the symptoms. 4 months after the accident, we had a stroke with right hemiparesis. This situation produced worsening of the dyspnea.

Physiotherapy was reinforced with recuperation of the hemiparesis, but poor improvement of the dyspnea.

10 months after the accident, surgery was indicated for plication of the diaphragm to improve the respiratory function.

Results

The video shows the radiological exams and the surgery performed. Laparoscopic diaphragmatic plication with a reinforcement with a coated mesh (Uncoated monofilament polypropylene mesh on the anterior side with an absorbable hydrogel barrier). He was discharge 2 days after surgery.

The patient improved significantly in his respiratory symptoms an imaging exams.

Conclusions

Posttraumatic DE must be treated surgically with low morbidity and good functional results.
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

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

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 >1 log10 IU/mL. HBV clinical reactivation was HBV virologic reactivation with alanine aminotransferase (ALT) >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 >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

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 >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 >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

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

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

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

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

L1CAMs 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

We 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

Azimuth 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

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.
COVID-19 as a Trigger for De Novo Crohn’s Disease
Authors: Tursi Antonio , Nenna Rosanna
Published: December 2021

Lay Summary

A 47-year-old woman developed a de novo occurrence of Crohn’s disease after coronavirus disease 2019. This is an unusual occurrence and suggests that severe acute respiratory syndrome coronavirus 2 could trigger inflammatory bowel disease in predisposed people.
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

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.
Effects of restricting energy during the gilt development period on growth and reproduction of lines differing in lean growth rate: responses in reproductive performance and longevity
Authors: Johnson Rodger K , Trenhaile-Grannemann Melanie D , Moreno Roman , Ciobanu Daniel C , Miller Phillip S
Published: December 2021

Longevity and reproductive performance are economically important traits in the swine industry that are largely influenced by nutrition and other environmental factors. Reproductive performance and longevity through 4 parities was assessed in gilts of 2 genetic lines developed on ad libitum access to feed or restricted to 75% of ad libitum intake. A total of 661 gilts were used in a 2 × 2 factorial with half of the gilts allocated to an ad libitum diet (AL; n = 330), while the other half were energy restricted by 25% (R; n = 331) from 123 to 235 d of age. All gilts were sired by an industry maternal line. Dams of the gilts were from either a Large White (W) by Landrace (L) industry maternal line or Nebraska Selection Line 45X, producing gilts designated as W × L (n = 355) and L45X (n = 306), respectively. Daily estrus detection began at 140 d of age to obtain age at puberty (AP). Gilts (n = 510) were mated on their second or later estrus, beginning at 240 d of age. Sow weight and backfat were recorded at 110 d of gestation and weaning of each parity. Number of live-born, stillborn, and mummified pigs per litter and piglet birth and weaning weights were recorded through 4 parities. More L45X than W × L and more AL than R gilts reached puberty by 230 d of age (P < 0.01). Dietary treatment did not affect probability to produce parities 1 to 4 or any litter trait analyzed. The L45X females tended to be more likely to produce parities 1 (P < 0.08) and 3 (P < 0.06), while W × L had heavier litters at birth (P < 0.01) and weaning (P = 0.01). Treatment by parity interactions (P < 0.01) existed for weight and backfat prior to farrowing and backfat at weaning, and weight at weaning exhibited a line by treatment by parity interaction (P = 0.04) as R sows had lower weights and backfats in earlier parities, but caught up to AL sows in later parities. A treatment by parity interaction (P < 0.01) was also present for backfat loss from farrowing to weaning as R gilts lost less backfat than AL in parities 1 and 2, but more in parities 3 and 4. No significant differences were detected between lines or treatments for lifetime production traits. The populations of pigs and data presented here provide a framework for a diverse array of further studies. Alternative approaches to restrict energy have been assessed in addition to methods of marker-assisted and genomic selection for improvement of litter size and sow longevity.
Postglacial colonization in the Great Lakes Region by the white-footed mouse (Peromyscus leucopus): conflicts between genomic and field data
Authors: Prado Joyce R , Rubi Tricia L , Baumgartner Joseph , Hoffman Susan M G , Dantzer Ben , Lacey Knowles L
Published: December 2021

For regions that were covered by ice during the Pleistocene glaciations, species must have emigrated from unglaciated regions. However, it can be difficult to discern when and from what ancestral source populations such expansions took place, especially since warming climates introduce the possibility of very recent expansions. For example, in the Great Lakes region, pronounced climatic change includes past glaciations as well as recent, rapid warming. Here we evaluate different expansion hypotheses with a genomic study of the white-footed mouse (Peromyscus leucopus noveboracensis), which is one of the most common mammals throughout the Great Lakes region. Ecological surveys coupled with historical museum records suggest a recent range expansion of P. leucopus associated with the warming climate over the last decades. These detailed records have yet to be complemented by genomic data that provide the requisite resolution for detecting recent expansion, although some mitochondrial DNA (mtDNA) sequences have suggested possible hypotheses about the geography of expansion. With more than 7,000 loci generated using RADseq, we evaluate support for multiple hypotheses of a geographic expansion in the Upper Peninsula of Michigan (UP). Analysis of a single random single-nucleotide polymorphism per locus revealed a fine-scale population structure separating the Lower Peninsula (LP) population from all other populations in the UP. We also detected a genetic structure that reflects an evolutionary history of postglacial colonization from two different origins into the UP, one coming from the LP and one coming from the west. Instead of supporting a climate-driven range expansion, as suggested by field surveys, our results support more ancient postglacial colonization of the UP from two different ancestral sources. With these results, we offer new insights about P. leucopus geographic expansion history, as well as a more general phylogeographic framework for testing range shifts in the Great Lakes region.
Tumor-Derived Cell Culture Model for the Investigation of Meningioma Biology
Authors: Uhlmann Erik J , Rabinovsky Rosalia , Varma Hemant , El Fatimy Rachid , Kasper Ekkehard M , Moore Justin M , Vega Rafael A , Thomas Ajith J , Alterman Ronald L , Stippler Martina , Anderson Matthew P , Uhlmann Erik N , Kipper Franciele C , Krichevsky Anna M
Published: December 2021

Meningioma is the most common primary central nervous system tumor. Although mostly nonmalignant, meningioma can cause serious complications by mass effect and vasogenic edema. While surgery and radiation improve outcomes, not all cases can be treated due to eloquent location. Presently no medical treatment is available to slow meningioma growth owing to incomplete understanding of the underlying pathology, which in turn is due to the lack of high-fidelity tissue culture and animal models. We propose a simple and rapid method for the establishment of meningioma tumor-derived primary cultures. These cells can be maintained in culture for a limited time in serum-free media as spheres and form adherent cultures in the presence of 4% fetal calf serum. Many of the tissue samples show expression of the lineage marker PDG2S, which is typically retained in matched cultured cells, suggesting the presence of cells of arachnoid origin. Furthermore, nonarachnoid cells including vascular endothelial cells are also present in the cultures in addition to arachnoid cells, potentially providing a more accurate tumor cell microenvironment, and thus making the model more relevant for meningioma research and high-throughput drug screening.
Creating and Disrupting Othering During Policymaking in a Polarized Context
Authors: Schraedley Megan K , Dougherty Debbie S
Published: December 2021

As the United States has become increasingly polarized, policymakers have had difficulty gaining bipartisan support for policy proposals. Political polarization can lead to the othering of individuals, a process characterized by the tendency to construct members of an opposing party in negative ways. In this article, we examine the creation and disruption of othering through the lens of language convergence/meaning divergence (LC/MD) and pragmatic ambiguity. LC/MD and pragmatic ambiguity framed our case study of the successful bipartisan passage of the Global Food Security Act (GFSA) in 2016. We found that othering was produced through a maestro Discourse of Polarization that structured interactions between other Discourses, including the Discourse of National Security and the Global Good Discourse. Discordant framings of the three Discourses created the ambiguity necessary to disrupt othering and achieve collective action. The findings provide new theoretical insights into othering processes while pragmatic ambiguity broadens LC/MD in important ways.
Systems-level analysis of the plasticity of the maize metabolic network reveals novel hypotheses in the nitrogen-use efficiency of maize roots
Authors: Seaver Samuel M D
Published: December 2021

This article comments on:

Chowdhury NB, Schroeder WL, Sarkar D, Amiour N, Quilleré I, Hirel B, Maranas CD, Saha R. 2022. Dissecting the metabolic reprogramming of maize root under nitrogen-deficient stress conditions. Journal of Experimental Botany 73, 275–291.
Hen 3-860: new southern eclipsing symbiotic star observed in the outburst
Authors: Merc J , Gális R , Wolf M , Velez P , Bohlsen T , Barlow B N
Published: December 2021

Brightening of Hen 3-860, previously classified as an Hα emitter, was detected by the All-Sky Automated Survey for Supernovae (ASAS-SN) survey at the end of the year 2016. We have obtained the first spectroscopic observations of the transient and supplemented them with photometric data from the Digital Access to a Sky Century at Harvard (DASCH) archive of astronomical plates, All-Sky Automated Survey (ASAS), and ASAS-SN surveys. Based on the results of our analysis, we can classify the object as a classical symbiotic star of the infrared type S, consisting of an M2-3 giant with a temperature of Tg ∼ 3550 K, a radius of Rg ∼ 60–75 R⊙, and a luminosity of Lg ∼ 540–760 L⊙, and a hot and luminous component (Th ∼ 1 × 105–2 × 105 K and $L_{\rm h}\, \sim 10^3\, L_\odot$). The system experienced at least four outbursts in the last 120 years. In addition to the outbursts, its light curves revealed the presence of eclipses of the hot component and its surrounding (relatively cool) shell, which developed during the outburst and redistributed a fraction of the radiation of the hot component into the optical, by the giant, classifying the object as a representative of a group of eclipsing symbiotic stars. The eclipses allowed us to reveal the orbital period of the system to be 602 d.
Constraining protoplanetary disc mass using the GI wiggle
Authors: Terry J P , Hall C , Longarini C , Lodato G , Toci C , Veronesi B , Paneque-Carreño T , Pinte C
Published: December 2021

Exoplanets form in protoplanetary accretion discs. The total protoplanetary disc mass is the most fundamental parameter, since it sets the mass budget for planet formation. Although observations with the Atacama Large Millimeter/Submillimeter array (ALMA) have dramatically increased our understanding of these discs, total protoplanetary disc mass remains difficult to measure. If a disc is sufficiently massive (≳10 per cent of the host star mass), it can excite gravitational instability (GI). Recently, it has been revealed that GI leaves kinematic imprints of its presence known as the ‘GI Wiggle’. In this work, we use numerical simulations to determine an approximately linear relationship between the amplitude of the wiggle and the host disc-to-star mass ratio, and show that measurements of the amplitude are possible with the spatial and spectral capabilities of ALMA. These measurements can therefore be used to constrain disc-to-star mass ratio.
Impact of denosumab discontinuation on changes in bone mineral density and bone erosion in rheumatoid arthritis patients
Authors: Tanaka Sakae , Kobayashi Makiko , Saito Kengo , Takita Atsushi
Published: December 2021

Objectives

This study investigated changes in bone mineral density (BMD) and erosion after denosumab discontinuation in rheumatoid arthritis (RA) patients without osteoporosis who participated in the DESIRABLE study.

Methods

This multicentre observational study consisted of a prediscontinuation visit (date of final assessment in DESIRABLE) and a postdiscontinuation visit (2.5 years after the last administered dose of denosumab). Percentage change in lumbar spine (LS) BMD from baseline was assessed as the primary endpoint.

Results

Fifty-nine patients were enrolled. The percentage change in LS BMD decreased to baseline levels at the postdiscontinuation visit. Compared with baseline, C-telopeptide of type I collagen levels increased after denosumab discontinuation but most patients had levels within the reference range. Bone erosion scores were not significantly different between the on-treatment period and after denosumab discontinuation (p = .0666) but there was a numerical increase postdiscontinuation. The progression in bone erosion score was significantly reduced in patients whose disease activity was in remission versus those not in remission (p = .0195).

Conclusions

In RA patients without osteoporosis, denosumab discontinuation can be explored while considering patient background factors (disease activity and risk of fracture) and accounting for progression of bone erosion and LS BMD decrease after withdrawal.
Identifying essential genes across eukaryotes by machine learning
Authors: Beder Thomas , Aromolaran Olufemi , Dönitz Jürgen , Tapanelli Sofia , Adedeji Eunice O , Adebiyi Ezekiel , Bucher Gregor , Koenig Rainer
Published: December 2021

Identifying essential genes on a genome scale is resource intensive and has been performed for only a few eukaryotes. For less studied organisms essentiality might be predicted by gene homology. However, this approach cannot be applied to non-conserved genes. Additionally, divergent essentiality information is obtained from studying single cells or whole, multi-cellular organisms, and particularly when derived from human cell line screens and human population studies. We employed machine learning across six model eukaryotes and 60 381 genes, using 41 635 features derived from the sequence, gene function information and network topology. Within a leave-one-organism-out cross-validation, the classifiers showed high generalizability with an average accuracy close to 80% in the left-out species. As a case study, we applied the method to Tribolium castaneum and Bombyx mori and validated predictions experimentally yielding similar performances. Finally, using the classifier based on the studied model organisms enabled linking the essentiality information of human cell line screens and population studies.