bluuebunny/crossref_metadata_2025 huggingface dataset:
O26 INFECTIOUS COMPLICATION IN RELATION TO THE PROPHYLACTIC MESH POSITION: THE PRIMA TRIAL REVISITED
Authors: Van den Dop Matthijs , Sneiders Dimitri , Kleinrensink Gert-Jan , Jeekel Hans , Lange Johan , Timmermans Lucas
Published: December 2021

Aim

Prophylactic mesh reinforcement has proven to reduce the incidence of incisional hernia (IH). Fear of infectious complications may withhold the widespread implementation of prophylactic mesh reinforcement, particularly in the onlay position.

Material and Methods

Patients scheduled for elective midline surgery were randomly assigned to a suture closure group, onlay mesh group, or sublay mesh group. The incidence, treatment, and outcomes of patients with infectious complications were assessed through examining the adverse event forms. Data were collected prospectively for 2 years after the index procedure.

Results

Overall, infectious complications occurred in 14/107 (13.3%) patients in the suture group and in 52/373 (13.9%) patients with prophylactic mesh reinforcement (p = 0.821). Infectious complications occurred in 17.6% of the onlay group and 10.3% of the sublay group (p = 0.042). Excluding anastomotic leakage as a cause, these incidences were 16% (onlay) and 9.7% (sublay), p = 0.073. The mesh could remain in-situ in 40/52 (77%) patients with an infectious complication. The 2-year IH incidence after onlay mesh reinforcement was 10 in 33 (30.3%) with infectious complications and 15 in 140 (9.7%) without infectious complications (p = 0.003). This difference was not statistically significant for the sublay group.

Conclusions

Prophylactic mesh placement was not associated with increased incidence, severity, or need for invasive treatment of infectious complications compared with suture closure. Patients with onlay mesh reinforcement and an infectious complication had a significantly higher risk of developing an incisional hernia, compared with those in the sublay group.
O35 WHAT HAPPENS TO PATIENTS WITH ACUTELY SYMPTOMATIC HERNIA IN THE UK? FINDINGS FROM THE MASH STUDY
Authors: Proctor Victoria , Spence Olivia , Burns Flora , Green Susanna , Sayers Adele , Smart Neil , Lee Matthew
Published: December 2021

Aim

Acutely symptomatic abdominal wall and groin hernias (ASH) are a common reason for acute surgical admissions in the UK. There is limited data to guide the treatment of such presentations. This study aimed to assess outcomes of emergency hernia surgery, and identify common management strategies, to improve care for these high-risk patients.

Material and Methods

A 12 week, UK-based, multi-centre, collaborative, prospective cohort study (NCT04197271) recruited adults with ASH. Data on patient characteristics, inpatient management, quality of life, complications and wound healing was collected. 30 and 90-day follow-up phone calls assessed complications and quality of life. Descriptive analyses were performed to describe population and outcomes.

Results

Twenty-three acute Trusts recruited 268 patients. Inguinal (37.7%) and umbilical (37.7%) were the most common hernia locations. 13.4% were awaiting elective surgery and 13.1% had been previously declined intervention. CT was performed in 48%. 82% underwent surgical management with open repair (94%) under general anaesthesia (93%) being most common. 4/11 laparoscopic procedures were converted to open. 55% of repairs used mesh, typically synthetic non-absorbable (87%). Complications were infrequent with surgical site infection (9.4%), delirium (3.2%) and pneumonia (2.3%) being most common. Mortality was 1.5%. Immediate surgical management was associated with significant improvement in quality of life at 30 days.

Conclusions

There is variation in the investigation, management and surgical strategy to treat acutely symptomatic abdominal wall and groin hernias in the UK. Further large-scale work is needed to establish the optimal management strategy for specific acute presentations given the wide variation at present.
O40 A MODIFIED DELPHI PROCESS TO ESTABLISH RESEARCH PRIORITIES IN HERNIA SURGERY
Authors: Scrimgeour Duncan , Allan Morven , East Barbora , Blackwell Sue , Laidlaw Lynn , Light Duncan , Smart Neil , Horgan Liam , Beaux Andrew de , Wilson Michael
Published: December 2021

Aim

Abdominal wall hernia repair is one of the most commonly performed surgical procedures worldwide, yet there remains a lack of high quality evidence to support best management. The aim of the study was to use a modified Delphi process to determine future research priorities in this field.

Material and Methods

Stakeholders were invited by email, using British Hernia Society membership details or Twitter, to submit individual research questions via an online survey. In addition, questions obtained from a patient focus group (PFG) were collated to form Phase I. Two rounds of prioritisation by stakeholders (phase II and III) were then completed to determine a final list of questions. All questions were analysed on an anonymised basis.

Results

A total of 266 questions, 19 from the PFG, were submitted by 113 stakeholders in Phase I. Of these, 64 questions were taken forward for prioritisation in Phase II, which was completed by 107 stakeholders. Following Phase II analysis, 97 stakeholders prioritised 36 questions in Phase III. This resulted in a final list of 14 research questions, 3 of which were from the PFG. Stakeholders included patients and healthcare professionals (consultant surgeons, trainee surgeons and other multidisciplinary members) from over 27 countries during the 3 phases. 

Conclusions

Fourteen key research priorities pertaining to abdominal wall hernia surgery were identified. Many topics focused on pain, mesh and what the optimal outcome measures following hernia surgery should be. Uniquely, these priorities have been determined from participation by both healthcare professionals and patients. These priorities should now be addressed by well-designed, high-quality international collaborative research.
O49 COMPARING OUTCOMES BETWEEN MINIMALLY INVASIVE AND OPEN INGUINAL HERNIA REPAIR
Authors: Katzen Michael , Ayuso Sullivan , Aladegbami Bola , Nayak Raageswari , Colavita Paul , Augenstein Vedra , Kercher Kent , Todd Heniford B
Published: December 2021

Aim

Prospective evaluation comparing outcomes between laparoscopic (LIHR), robotic (RIHR), and open inguinal hernia repair (OIHR).

Material and Methods

Prospective institutional data comparison of patients undergoing inguinal hernia repair from 1999–2020 was performed. Patients with chronic pain or infection were excluded. Standard statistical methods were used and univariate analysis was performed between LIHR, RIHR, and OIHR groups.

Results

3,300 repairs were performed: 1,970 LIHR (597-bilateral), 127 RIHR (25-bilateral), and 538 OIHR (43-bilateral). LIHR and RIHR patients were younger (55.4±14.8vs59.0±13.7vs 65.0±13.7years;p<0.01), with lower BMI (26.6±6.5vs28.9±20.3vs31.8±7.6kg/m2; p<0.01), fewer overall (2.7±1.9 vs 2.7±2.2vs3.7±2.5; p < 0.01) and cardiac (0.2% vs 0% vs 2.6%; p<0.01) comorbidities, and fewer patients had diabetes (5.2%vs4.6%vs10.9%; p<0.01). OIHR had the highest rate of recurrent hernias (21.2%vs11.2%vs30.9%; p<0.01). History of smoking was less in LIHR (13.9%vs30.9%vs19.5%%; p<0.01). Mesh was used in 99.5% of cases; synthetic was used in all minimally invasive cases and 98.4% of OIHR, with biologic mesh in 1.0% of OIHR due to bowel resection during the operation. Operative time was shortest in LIHR followed by open (86.5±39.6vs109.0±56.8vs92.6±55.2 min; p<0.01). Wound complications were more frequent in OIHR (0.8%vs0.7%vs3.8%; p<0.01). Admission was more common after open repair (2.2%vs2.7%vs5.7%; p<0.01) with a trend to less readmission following LIHR (1.0%vs2.0%vs2.3%; p=0.06). There were few recurrences overall (0.7%vs0.7%vs1.3%; p=0.40) with mean follow-up time 21.1±22.4 months.

Conclusions

LIHR, RIHR, and OIHR were performed with low overall morbidity and complications. Recurrent hernias and cardiac patients were most often repaired open, which more frequent admission and had higher wound morbidity. RIHR had longer OR times with no improvement overall outcomes.
OV02 COMPLEX PARASTOMAL HERNIA REPAIR WITH MESH FISTULA AND MESH INFECTION
Authors: Elhage Sharbel , Deerenberg Eva , Ayuso Sullivan , Augenstein Vedra , Kasten Kevin , Todd Heniford B
Published: December 2021

Aim

Parastomal hernias of any size can be difficult to manage and greatly affect a patient’s quality of life, however, they can be even more problematic when associated with loss of domain and infection. The aim of our video was to demonstrate open repair of a massive parastomal hernia complicated by loss of domain, mesh fistula, and mesh infection.

Material and Methods

Images and footage from clinic and the operative procedure were included.

Results

A 51-year-old female with a history of prior APR followed by failed ventral and parastomal hernia repairs presented with a massive parastomal hernia that was significantly impacting her and her family’s quality of life. Due to her hernia, she had become immobile and was bed bound. Furthermore, the hernia had caused significant chronic constipation secondary to colonic dysmotility. The patient also had loss of domain, and her hernia appeared to be complicated by a chronic mesh infection with a draining sinus. She underwent pre-operative bilateral botulinum toxin A injection in the oblique abdominal musculature. She then underwent open preperitoneal parastomal hernia repair with biologic mesh, excision of prior mesh, primary fistula repair, total abdominal colectomy, and end ileostomy. The patient tolerated the procedure well without complications and has continued to do well in follow-up. She has had great improvement in her quality of life.

Conclusions

In this patient with a massive parastomal hernia complicated by loss of domain, mesh fistula, and mesh infection, we demonstrate a successful open preperitoneal repair following pre-operative BTA injection.
OV10 LAPAROSCOPIC-GUIDED TRANSVERSUS ABDOMINIS PLANE (TAP) BLOCK IN HERNIA SURGERY - HOW WE DO IT
Authors: Gonçalves Mário Rui , Antunes Conceição , Capinha Mariana , Arantes Ana Rita , Almeida Paulo , Pereira Joaquim Costa
Published: December 2021

Aim

“COVID has been a great challenge for Hospitals around the world. At our surgical department a new protocol of TAP block was designed and implemented in our laparoscopic incisional ventral hernia repairs, to allow these patients to be operated in ambulatory regime, without compromising pain control and the outcomes. In this video we aim to present the technique for the Laparoscopic-guided TAP Block during a Laparoscopic IPOM Plus ventral hernia repair.”

Material and Methods

“We implemented this protocol in July 2020 and since then, we performed 18 TAP block in laparoscopic incisional hernia repairs, laparoscopic guided by the Surgeon or ultrasound-guided by the Anesthesiologist. In this case, the video reports to a Laparoscopic IPOM Plus incisional hernia repair performed on a 54-year-old patient, male, with obesity, arterial hypertension and dyslipidemia. He had a 6 centimeter incisional hernia post-colorectal surgery in 2013.”

Results

“As detailed in the video, we show all the steps to perform a TAP block under laparoscopic direct visualization”

Conclusions

“TAP block can be performed by the Surgeon, with direct visualization at the beginning of the laparoscopic procedure.”
The Effect of Antiretroviral Therapy for the Treatment of Human Immunodeficiency Virus (HIV)-1 in Pregnancy on Gestational Weight Gain
Authors: Joseph Naima T , Satten Glen A , Williams Rachel E , Haddad Lisa B , Jamieson Denise J , Sheth Anandi N , Badell Martina L
Published: December 2021

Background

Gestational weight gain above Institute of Medicine recommendations is associated with increased risk of pregnancy complications. The goal was to analyze the association between newer HIV antiretroviral regimens (ART) on gestational weight gain.

Methods

A retrospective cohort study of pregnant women with HIV-1 on ART. The primary outcome was incidence of excess gestational weight gain. Treatment effects were estimated by ART regimen type using log-linear models for relative risk (RR), adjusting for prepregnancy BMI and presence of detectable viral load at baseline.

Results

Three hundred three pregnant women were included in the analysis. Baseline characteristics, including prepregnancy BMI, viral load at prenatal care entry, and gestational age at delivery were similar by ART, including 53% of the entire cohort had initiated ART before pregnancy (P = nonsignificant). Excess gestational weight gain occurred in 29% of the cohort. Compared with non–integrase strand transfer inhibitor (-INSTI) or tenofovir alafenamide fumarate (TAF)–exposed persons, receipt of INSTI+TAF showed a 1.7-fold increased RR of excess gestational weight gain (95% CI: 1.18–2.68; P < .01), while women who received tenofovir disoproxil fumarate had a 0.64-fold decreased RR (95% CI: .41–.99; P = .047) of excess gestational weight gain. INSTI alone was not significantly associated with excess weight gain in this population. The effect of TAF without INSTI could not be inferred from our data. There was no difference in neonatal, obstetric, or maternal outcomes between the groups.

Conclusions

Pregnant women receiving ART with a combined regimen of INSTI and TAF have increased risk of excess gestational weight gain.
Nonparametric bounds on treatment effects with imperfect instruments
Authors: Ban Kyunghoon , Kédagni Désiré
Published: December 2021

This paper extends the identification results in Nevo and Rosen (2012) to nonparametric models. We derive nonparametric bounds on the average treatment effect when an imperfect instrument is available. As in Nevo and Rosen (2012), we assume that the correlation between the imperfect instrument and the unobserved latent variables has the same sign as the correlation between the endogenous variable and the latent variables. We show that the monotone treatment selection and monotone instrumental variable restrictions, introduced by Manski and Pepper (2000; 2009), jointly imply this assumption. Moreover, we show how the monotone treatment response assumption can help tighten the bounds. The identified set can be written in the form of intersection bounds, which is more conducive to inference. We illustrate our methodology using the National Longitudinal Survey of Young Men data to estimate returns to schooling.
Artificial intelligence analysis of three-dimensional imaging data derives factors associated with postoperative recurrence in patients with radiologically solid-predominant small-sized lung cancers
Authors: Kudo Yujin , Shimada Yoshihisa , Matsubayashi Jun , Kitamura Yoshiro , Makino Yojiro , Maehara Sachio , Hagiwara Masaru , Park Jinho , Yamada Takafumi , Takeuchi Susumu , Kakihana Masatoshi , Nagao Toshitaka , Ohira Tatsuo , Masumoto Jun , Ikeda Norihiko
Published: December 2021

OBJECTIVES

Indications of limited resection, such as segmentectomy, have recently been reported for patients with solid-predominant lung cancers ≤2 cm. This study aims to identify unfavourable prognostic factors using three-dimensional imaging analysis with artificial intelligence (AI) technology.

METHODS

A total of 157 patients who had clinical N0 non-small cell lung cancer with a radiological size ≤2 cm, and a consolidation tumour ratio > 0.5, who underwent anatomical lung resection between 2011 and 2017 were enrolled. To evaluate the three-dimensional structure, the ground-glass nodule/Solid Automatic Identification AI software Beta Version (AI software; Fujifilm Corporation, Japan) was used.

RESULTS

Maximum standardized uptake value (SUVmax) and solid-part volume measured by AI software (AI-SV) showed significant differences between the 139 patients with adenocarcinoma and the 18 patients with non-adenocarcinoma. Among the adenocarcinoma patients, 42 patients (30.2%) were found to be pathological upstaging. Multivariable analysis demonstrated that high SUVmax, high carcinoembryonic antigen level and high AI-SV were significant prognostic factors for recurrence-free survival (RFS; P < 0.05). The 5-year RFS was compared between patients with tumours showing high SUVmax and those showing low SUVmax (67.7% vs 95.4%, respectively, P < 0.001). The 5-year RFS was 91.0% in patients with small AI-SV and 68.1% in those with high AI-SV (P = 0.001).

CONCLUSIONS

High AI-SV, high SUVmax and abnormal carcinoembryonic antigen level were unfavourable prognostic factors of patients with solid-predominant lung adenocarcinoma with a radiological size ≤2 cm. Our results suggest that lobectomy should be preferred to segmentectomy for patients with these prognostic factors.
C1. A “ Ping-Pong ” Ball Left Atrial Thrombus Mimicking Left Atrial Myxoma : A Case Report
Authors: Hargiyanto E D , Baktijasa B
Published: December 2021

Background

Valvular heart disease has a high prevalence, especially in developing countries, even though there is actually no exact number for prevalence in Indonesia. The prevalence of left atrial thrombus is around 17% in patients with severe mitral stenosis and will increase about 2 times in patients with atrial fibrillation. Although left atrial thrombus is common in mitral stenosis, left atrial thrombus mimicking myxoma is rarely reported

Case Summary

47-year-old woman came to Dr. Soetomo cardiology outpatient clinic. She complained of palpitation and shortness of breath. Her electrocardiogram was showed atrial fibrillation. Echocardiography showed severe mitral stenosis and free moving, round shape, left atrial mass. She then immediately planned for Mitral Valve Replacement (MVR) surgery and evacuation of the mass. We found a solid wall spherical mass, layered and easily separate. Microscopic examination revealed extensive fibrin, hemorrhage and mononuclear inflammatory cells with the conclusion of a thrombus

Discussion

Left atrial thrombus and myxoma often look the same on echocardiography, especially when the thrombus is free-moving and round shape. Echocardiography in this case showed a free-moving mass, round shape, like a "ping-pong" ball. The mass also has solid wall suggesting a myxoma. After surgery, we found tha the mass is multilayered which looks like a myxoma. However, microscopically confirmed that the mass is a thrombus. This suggests that a left atrial thrombus may mimicking a myxoma on echocardiography. Therefore, the gold standard for diagnosing intracardiac mass is by histopathology
Implantable cardioverter-defibrillators for hypertrophic cardiomyopathy: The Times They Are a-Changin’
Authors: Francia Pietro , Olivotto Iacopo , Lambiase Pier D , Autore Camillo
Published: December 2021

The implantable cardioverter-defibrillator (ICD) is a life-saving therapy in patients with hypertrophic cardiomyopathy (HCM) at high risk of sudden cardiac death. The heterogeneity of clinical scenarios in HCM and the availability of ICDs with distinct characteristics emphasizes the need for selecting the right device for the right patient. There is growing awareness that unnecessarily complex devices can lead to short- and long-term complications without adding significant clinical benefits. Young patients have the greatest potential years of life gained from the ICD but are also most exposed to device-related complications. This increases the complexity of decision-making of ICD prescription in these often otherwise well patients in whom device selection should be tailored to preserve survival benefit without introducing morbidity. In the light of the multiple clinical phenotypes characterizing HCM, the present article offers evidence-based perspectives helpful in predicting the individual impact of the ICD and choosing the most appropriate device.
‘Mead from Riga’: The Trade and Consumption of a Hanse Cultural Good in the Late Medieval Baltic
Authors: Whelan Mark
Published: December 2021

This article represents the first study of the trade and consumption of mead, the alcoholic beverage brewed by fermenting honey with water, in the late medieval Baltic. Focusing on the Teutonic Order and the Hanse settlements in the region, the article argues that the consumption of mead was culturally embedded in German-speaking communities, heightening the status of the beverage, turning it into a vital resource in the exercise of power and influencing the government and administrations of cities and lordships. From a broader perspective, a close study of the drink underlines the cultural and economic significance attached to bee produce in the later medieval period, with ecology and cultural practice combining to make honey and its pre-eminent product, mead, a distinctive international export that enjoyed high esteem and significant demand across Hanse trading networks.
Local Law for Singular Values of Oscillatory Matrices
Authors: Adhikari Arka , Lemm Marius
Published: December 2021

We continue the study of spectra of oscillatory random matrices with fully dependent rows. Motivated by the $d$-dimensional skew-shift dynamics from ergodic theory, we introduce the $N\times N$ random matrices $$ \begin{align*} &X_{j,k}=\exp\left(2\pi \textrm{i} \sum_{q=1}^d\ \omega_{j,q} k^q\right), \end{align*}$$where $\{\omega _{j,q}\}_{1\leq j\leq N, 1\leq q\leq d}$ is a collection of i.i.d. random variables and $d$ is a fixed integer. We prove that as $N\to \infty $ the distribution of singular values converges to the local Marchenko–Pastur law up to scales $N^{-\theta _d}$ for an explicit $\theta _d>0$, as long as $d\geq 18$. Our approach provides a novel mechanism—deterministic oscillatory cancellations—for universal spectral laws. The proof blends techniques from random matrix theory, harmonic analysis, and analytic number theory such as strong estimates on the number of solutions to Diophantine equations in the form of Vinogradov’s main conjecture, proved by Bourgain–Demeter–Guth.
Effects of dietary spray-dried plasma protein on nutrient digestibility and growth performance in nursery pigs
Authors: Kim Hansol , Lee Seung Hyung , Kim Beob Gyun
Published: December 2021

The objectives were to determine the digestible energy and standardized ileal digestibility of amino acids (AA; Exp. 1) and to determine growth performance (Exp. 2) of two sources of dietary spray-dried plasma protein (SDPP) in nursery pigs. In Exp. 1, twelve nursery barrows (9.8 ± 0.9 kg) were assigned to a quadruplicated 3 × 2 Latin square design with three diets and two periods. Each period consisted of 5 d of adaptation, 2 d of fecal sampling, and 2 d of ileal collection. A basal diet was composed of corn, soybean meal, whey, and sucrose as the sole energy and AA sources. Experimental diets were prepared by replacing 15% of the energy and AA sources in the basal diet with SDPP 1 (manufactured in the United States; 78.2% crude protein and 4,862 kcal gross energy/kg as-is) or SDPP 2 (manufactured in Korea; 74.3% crude protein and 4,636 kcal gross energy/kg as-is). Spray-dried plasma protein 1 had greater digestible energy (P < 0.05), but less (P < 0.05) standardized ileal digestibility of Lys, Met, Trp, and Thr compared with SDPP 2. In Exp. 2, eighty-four nursery pigs (7.9 ± 0.7 kg) were allotted to three dietary treatments in a randomized complete block design with seven replicate pens and four pigs per pen. Three corn–soybean meal–whey–based diets contained fish meal (6% and 3.5% for days 0 to 14 and 14 to 28, respectively), SDPP 1 (4.5% and 2.7%), or SDPP 2 (5.0% and 3.0%) to maintain same energy and nutrient concentrations. During days 0 to 14 and overall period, pigs fed the diets containing SDPP gained more weight (P < 0.05) than those fed the fish meal diet with no difference between two SDPP sources. In conclusion, SDPP 1 contains greater digestible energy but less AA digestibility compared with SDPP 2. Growth-promoting effects of both SDPP sources in nursery diets have been clearly demonstrated in this work.
Micelle silymarin supplementation to sows’ diet from day 109 of gestation to entire lactation period enhances reproductive performance and affects serum hormones and metabolites
Authors: Zhang Qianqian , Ahn Je Min , Kim In Ho
Published: December 2021

The aim of the present study was to explore the influences of varying doses of micelle silymarin (0%, 0.05%, 0.1%, and 0.2%) supplementation on sows’ feed intake, milk yields, serum hormones, and litter growth using 40 multiparous sows (Landrace × Yorkshire, parity from 3 to 5) from the 109th prenatal day to the 21st postnatal day. Each treatment included 10 sows and each sow was used as an experimental unit. On weaning day, litter weight and litter weight gain were linearly improved (P < 0.01, both), corresponding to the increasing dose of silymarin micelle in the diet. Also, litter weight, litter weight gain, and average daily gain (ADG) of piglets born to treated sows exceeded (P < 0.05) those of offspring from the control sows (0% micelle silymarin). Feed intake in week 1, week 2, and the entire lactation period was increased (linear, P < 0.01) as micelle silymarin dose increased. Body weight (BW) loss of sows during lactation was linearly reduced (P = 0.003) with the increasing amounts of micelle silymarin. Average daily milk yields during lactation were also linearly increased (P = 0.002) in treated sows, exceeding (P = 0.046) that of control sows. Also, uniform increases were observed (P = 0.037) in fat content in milk produced by treated sows on day 14 of lactation. Epinephrine concentrations and aspartate aminotransferase (AST) activity in sow serum on day 21 postpartum were linearly declined (P = 0.010) as micelle silymarin dose increased, and were both declined (P < 0.05) in treated sows compared with the control. In addition, treated sows’ serum had higher activity of superoxide dismutase (SOD) at parturition and glutathione peroxidase (GSH-Px), lower oxidized glutathione (GSSG) concentrations, and GSSG/GSH (glutathione) ratio (all, P < 0.01) on day 21 of lactation. Moreover, offspring from micelle silymarin-treated sows tended to (0.05 < P <0.1) have higher serum catalase (CAT) activity and total antioxidant capacity (T-AOC) concentrations. Taken together, the results showed that sows fed increasing levels of micelle silymarin from the 109th prenatal day to the 21st postnatal day had an incremental dose-dependent effect on higher feed intake, diminished BW loss, greater milk yields, and greater litter weight at weaning, and 0.2% of micelle silymarin could be optimal to achieve the better effect.
Novel RAF Fusions in Pediatric Low-Grade Gliomas Demonstrate MAPK Pathway Activation
Authors: Lind Katherine T , Chatwin Hannah V , DeSisto John , Coleman Philip , Sanford Bridget , Donson Andrew M , Davies Kurtis D , Willard Nicholas , Ewing Calvin A , Knox Aaron J , Mulcahy Levy Jean M , Gilani Ahmed , Green Adam L
Published: December 2021

Brain tumors are the most common solid tumor in children, and low-grade gliomas (LGGs) are the most common childhood brain tumor. Here, we report on 3 patients with LGG harboring previously unreported or rarely reported RAF fusions: FYCO1-RAF1, CTTNBP2-BRAF, and SLC44A1-BRAF. We hypothesized that these tumors would show molecular similarity to the canonical KIAA1549-BRAF fusion that is the most widely seen alteration in pilocytic astrocytoma (PA), the most common pediatric LGG variant, and that this similarity would include mitogen-activated protein kinase (MAPK) pathway activation. To test our hypothesis, we utilized immunofluorescent imaging and RNA-sequencing in normal brain, KIAA1549-BRAF-harboring tumors, and our 3 tumors with novel fusions. We performed immunofluorescent staining of ERK and phosphorylated ERK (p-ERK), identifying increased p-ERK expression in KIAA1549-BRAF fused PA and the novel fusion samples, indicative of MAPK pathway activation. Geneset enrichment analysis further confirmed upregulated downstream MAPK activation. These results suggest that MAPK activation is the oncogenic mechanism in noncanonical RAF fusion-driven LGG. Similarity in the oncogenic mechanism suggests that LGGs with noncanonical RAF fusions are likely to respond to MEK inhibitors.
The Return of Biblical Theology: Rabbi Lord Jonathan Sacks and the Theological-Literary Movement
Authors: Jotkowitz Alan
Published: December 2021

Lord Rabbi Jonathan Sacks, the former Chief Rabbi of the British Empire, is probably the most important and well-known Jewish theologian of the twenty-first century. He believed passionately that Jewish values have relevance for all of mankind. What is somewhat surprising is the source of R. Sacks's theology. Orthodox Jewish theology has traditionally been anchored in either the perspective of Talmudic Rabbis as transmitted through the halacha and the aggadda, or based on the works of the great medieval Jewish philosophers such as the Rambam, Crescas and Yehuda Halevi. In contradistinction to these approaches, R. Sacks turned to the Bible as the primary source of his theology. This “returning to the bible” is consistent with other trends in orthodox Jewish scholarship which also emphasizes a return to intensive study of the biblical text using modern methodologies. However, since biblical theology is open to a myriad of differing and even contradictory opinions, the role of rabbinic tradition is of utmost importance. Thus, for Rabbi Sacks's theology to have lasting impact it needs to be based on, and a natural extension of, the timeless Jewish tradition. This essay will explore these issues.
Evaluation of the classification of pre-solar silicon carbide grains using consensus clustering with resampling methods: An assessment of the confidence of grain assignments
Authors: Hystad Grethe , Boujibar Asmaa , Liu Nan , Nittler Larry R , Hazen Robert M
Published: December 2021

We report the use of several cluster analysis techniques to evaluate the classification of pre-solar silicon carbide (SiC) grains. The stability of clusters and the confidence of individual cluster assignments of grains are assessed using consensus clustering with resampling methods. Our analysis shows that pre-solar SiC grains can be divided into seven groups that are found to be highly stable with most of the grains being assigned to the same cluster for at least 90 per cent of the time over multiple aggregated clustering. Among the seven groups, two groups are dominated by AB grains, three groups by MS grains, one group by Z grains, and one group by X grains. The further division of X grains into two groups is highly dependent on the chosen algorithm and is therefore uncertain. Z and Y grains are clustered jointly with MS grains, with one group dominated by Z grains, pointing to their common origins from low-mass asymptotic giant branch stars. The most stable N grain-containing clusters are dominated by 15N-rich AB grains. However, some methods assign N grains with X grains, but in less stable clusters. The suggested genetic relationship among 15N-rich AB, N, and X grains is in line with the recent proposal that all three types of pre-solar SiC grains came from core collapse supernovae. We discuss the results from different clustering techniques based on our assessment of the cluster stabilities and the extent to which the cluster assignments overlap across the different methods.
The GALAH Survey: chemical tagging and chrono-chemodynamics of accreted halo stars with GALAH+ DR3 andGaiaeDR3
Authors: Buder Sven , Lind Karin , Ness Melissa K , Feuillet Diane K , Horta Danny , Monty Stephanie , Buck Tobias , Nordlander Thomas , Bland-Hawthorn Joss , Casey Andrew R , De Silva Gayandhi M , D’Orazi Valentina , Freeman Ken C , Hayden Michael R , Kos Janez , Martell Sarah L , Lewis Geraint F , Lin Jane , Schlesinger Katharine J , Sharma Sanjib , Simpson Jeffrey D , Stello Dennis , Zucker Daniel B , Zwitter Tomaž , Ciucă Ioana , Horner Jonathan , Kobayashi Chiaki , Ting (丁源森) Yuan-Sen , Wyse Rosemary F G ,   the GALAH collaboration
Published: December 2021

Since the advent of Gaia astrometry, it is possible to identify massive accreted systems within the Galaxy through their unique dynamical signatures. One such system, Gaia-Sausage-Enceladus (GSE), appears to be an early ‘building block’ given its virial mass $\gt 10^{10}\, \mathrm{M_\odot }$ at infall (z ∼ 1−3). In order to separate the progenitor population from the background stars, we investigate its chemical properties with up to 30 element abundances from the GALAH+ Survey Data Release 3 (DR3). To inform our choice of elements for purely chemically selecting accreted stars, we analyse 4164 stars with low-α abundances and halo kinematics. These are most different to the Milky Way stars for abundances of Mg, Si, Na, Al, Mn, Fe, Ni, and Cu. Based on the significance of abundance differences and detection rates, we apply Gaussian mixture models to various element abundance combinations. We find the most populated and least contaminated component, which we confirm to represent GSE, contains 1049 stars selected via [Na/Fe] versus [Mg/Mn] in GALAH+ DR3. We provide tables of our selections and report the chrono-chemodynamical properties (age, chemistry, and dynamics). Through a previously reported clean dynamical selection of GSE stars, including $30 \lt \sqrt{J_R / \, \mathrm{kpc\, km\, s^{-1}}} \lt 55$, we can characterize an unprecedented 24 abundances of this structure with GALAH+ DR3. With our chemical selection we characterize the dynamical properties of the GSE, for example mean $\sqrt{J_R / \, \mathrm{kpc\, km\, s^{-1}}} =$$26_{-14}^{+9}$. We find only $(29\pm 1){{\ \rm per\ cent}}$ of the GSE stars within the clean dynamical selection region. Our methodology will improve future studies of accreted structures and their importance for the formation of the Milky Way.
MODOMICS: a database of RNA modification pathways. 2021 update
Authors: Boccaletto Pietro , Stefaniak Filip , Ray Angana , Cappannini Andrea , Mukherjee Sunandan , Purta Elżbieta , Kurkowska Małgorzata , Shirvanizadeh Niloofar , Destefanis Eliana , Groza Paula , Avşar Gülben , Romitelli Antonia , Pir Pınar , Dassi Erik , Conticello Silvestro G , Aguilo Francesca , Bujnicki Janusz M
Published: December 2021

The MODOMICS database has been, since 2006, a manually curated and centralized resource, storing and distributing comprehensive information about modified ribonucleosides. Originally, it only contained data on the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. Over the years, prompted by the accumulation of new knowledge and new types of data, it has been updated with new information and functionalities. In this new release, we have created a catalog of RNA modifications linked to human diseases, e.g., due to mutations in genes encoding modification enzymes. MODOMICS has been linked extensively to RCSB Protein Data Bank, and sequences of experimentally determined RNA structures with modified residues have been added. This expansion was accompanied by including nucleotide 5′-monophosphate residues. We redesigned the web interface and upgraded the database backend. In addition, a search engine for chemically similar modified residues has been included that can be queried by SMILES codes or by drawing chemical molecules. Finally, previously available datasets of modified residues, biosynthetic pathways, and RNA-modifying enzymes have been updated. Overall, we provide users with a new, enhanced, and restyled tool for research on RNA modification. MODOMICS is available at https://iimcb.genesilico.pl/modomics/.
Zebularine induces enzymatic DNA–protein crosslinks in 45S rDNA heterochromatin of Arabidopsis nuclei
Authors: Prochazkova Klara , Finke Andreas , Tomaštíková Eva Dvořák , Filo Jaroslav , Bente Heinrich , Dvořák Petr , Ovečka Miroslav , Šamaj Jozef , Pecinka Ales
Published: December 2021

Loss of genome stability leads to reduced fitness, fertility and a high mutation rate. Therefore, the genome is guarded by the pathways monitoring its integrity and neutralizing DNA lesions. To analyze the mechanism of DNA damage induction by cytidine analog zebularine, we performed a forward-directed suppressor genetic screen in the background of Arabidopsis thaliana zebularine-hypersensitive structural maintenance of chromosomes 6b (smc6b) mutant. We show that smc6b hypersensitivity was suppressed by the mutations in EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 3 (ENT3), DNA METHYLTRANSFERASE 1 (MET1) and DECREASE IN DNA METHYLATION 1 (DDM1). Superior resistance of ent3 plants to zebularine indicated that ENT3 is likely necessary for the import of the drug to the cells. Identification of MET1 and DDM1 suggested that zebularine induces DNA damage by interference with the maintenance of CG DNA methylation. The same holds for structurally similar compounds 5-azacytidine and 2-deoxy-5-azacytidine. Based on our genetic and biochemical data, we propose that zebularine induces enzymatic DNA–protein crosslinks (DPCs) of MET1 and zebularine-containing DNA in Arabidopsis, which was confirmed by native chromatin immunoprecipitation experiments. Moreover, zebularine-induced DPCs accumulate preferentially in 45S rDNA chromocenters in a DDM1-dependent manner. These findings open a new avenue for studying genome stability and DPC repair in plants.
Deriving on-shell open string field amplitudes without using Feynman rules
Authors: Masuda Toru , Matsunaga Hiroaki
Published: December 2021

We present a series of new gauge-invariant quantities in Witten’s open string field theory. They are defined for a given set of open string states which satisfy the physical state condition around a classical solution. For known classical solutions, we demonstrate that these gauge-invariant quantities compute on-shell tree-level scattering amplitudes around the corresponding D-brane configuration.
P2P Lenders versus Banks: Cream Skimming or Bottom Fishing?
Authors: de Roure Calebe , Pelizzon Loriana , Thakor Anjan
Published: December 2021

We derive three testable predictions from a bank-P2P lender model of competition: (a) P2P lending grows when some banks are faced with exogenously higher regulatory costs; (b) P2P loans are riskier than bank loans; and (c) the risk-adjusted interest rates on P2P loans are lower than those on bank loans. We test these predictions against data on P2P loans and the consumer bank credit market in Germany and find empirical support. Overall, our analysis indicates that P2P lenders are bottom fishing, especially when regulatory shocks create a competitive disadvantage for some banks. (JEL G21)
Recovering Investor Expectations from Demand for Index Funds
Authors: Egan Mark , MacKay Alexander , Yang Hanbin
Published: December 2021

We use a revealed-preference approach to estimate investor expectations of stock market returns. Using data on demand for index funds that follow the S&P 500, we develop and estimate a model of investor choice to flexibly recover the time-varying distribution of expected future returns across investors. Our analysis is facilitated by the prevalence of leveraged funds that track the same underlying asset: by choosing between higher and lower leverage, investors trade off higher return against less risk. Our estimates indicate that investor expectations are heterogeneous, extrapolative, and persistent. Following a downturn, investors become more pessimistic on average, but there is also an increase in disagreement among participating investors due to the presence of contrarian investors.
A tribute to Robert Croyle, PhD, Director, Division of Cancer Control and Population Sciences
Authors: Rimer Barbara K
Published: December 2021

At the beginning of Dr. Robert Croyle’s 18th and final year as director of the National Cancer Institute’s (NCI) Division of Cancer Control and Population Sciences (DCCPS), before his retirement in December 2021, it is fitting to review some of his and the division’s many accomplishments and pay tribute to him as one of the government’s most effective leaders. The focus of this article is on Dr. Croyle’s contributions in the behavioral and related domains and his and the division’s impact on the landscape of cancer control and population sciences. Dr. Croyle joined DCCPS in 1998 as associate director for behavioral research. He became acting director of DCCPS in 2001 and then director in 2003. DCCPS is a formidable NCI division, with broad mandates and responsibilities and many partners from multiple sectors. The division conducts and supports an integrated program of the highest-quality genetic, epidemiological, behavioral, social, applied, survivorship, surveillance, and health care delivery cancer research. The division’s notable successes in implementation science and the dissemination of evidence-based findings and products, use of cancer research consortia, and partnerships across National Institutes of Health and with external federal and nongovernmental organizations are among many that reflect Dr. Croyle’s visionary leadership.
The new genus Aglaona: the first abyssal aglajid (Heterobranchia: Cephalaspidea: Aglajidae) with a description of two new species from the north-western Pacific Ocean
Authors: Chaban Elena M , Ekimova Irina A , Schepetov Dimitry M , Chernyshev Alexei V
Published: December 2021

In this paper we describe the new genus Aglaona, the first abyssal genus of the family Aglajidae, comprising two new species: Aglaona rudmani sp. nov. from the Sea of Okhotsk (inhabiting a depth of 3206 m) and Aglaona valdesi sp. nov. from the Pacific slope of the Kuril Islands (at a depth of 3374–3580 m). For species descriptions and inference of relationships, we have followed an integrative approach, including molecular phylogenetic analyses based on four markers (COI, 16S, H3 and 28S) and a morphological analysis based on traditional anatomical dissections and scanning electron microscopy. The new genus is characterized by a well-developed radula with marginal teeth (2:1:0:1:2) and an internal bulloid shell with a wing-like parietal callus. External and internal morphology of Aglaonagen. nov. species is similar to that of the philinoid genus Laona (family Laonidae). Phylogenetic analyses support the inclusion of the new genus in the family Aglajidae, but its sister-relationships are unresolved. Our results suggest that Aglaonagen. nov. possesses several plesiomorphic characters, and that the reduction of shell and radula in Aglajidae occurred in parallel in different lineages.
Pharmacokinetic interactions of modern antiretroviral therapy
Authors: Sinxadi Phumla Z. , Khoo Saye H. , Boffito Marta
Published: December 2021

Drug--drug interactions (DDIs) have been a clinical challenge in HIV medicine for over two decades. The newer antiretroviral drugs (ARTs) have significantly fewer DDIs than protease inhibitors and boosted integrase inhibitors (INSTIs). The lower propensity of such newer antiretrovirals (e.g. unboosted integrase inhibitors; doravirine) to cause DDIs, has been largely offset by the ageing cohort of patients with multiple comorbidities, who are taking multiple chronic medicines. Furthermore, the introduction of newly marketed drugs into clinical practice needs to be closely monitored, as the new drugs may be perpetrators of DDIs, leading to a potential change in the efficacy or toxicity of the coadministered antiretrovirals.
What we have learned from antiretroviral treatment optimization efforts over the last 5 years?
Authors: Venter W.D. Francois , Serenata Celicia , Vitoria Marco , Mkhondwane Luckyboy , Sikwese Kenly , Pepperrell Toby , Clayden Polly , Qavi Ambar , Doherty Meg , Penazzato Martina , Hill Andrew
Published: December 2021

Progression in the development of antiretroviral therapy has been remarkable, with new agents continuing to appear as options for modern regimens, including in low-and-middle income countries where the HIV epidemic is concentrated. Here, we reflect on progress made in guiding regimen changes to public health programmes, and the challenges facing selection of newer agents.
Dynamic Aphasia as a Variant of Frontotemporal Dementia
Authors: Chandregowda Adithya , Clark Heather M. , Duffy Joseph R. , Machulda Mary M. , Lowe Val J. , Whitwell Jennifer L. , Josephs Keith A.
Published: December 2021

We describe two individuals with progressive verbal difficulty who exhibited impairment of propositional language, with relatively well-preserved auditory comprehension, naming, and repetition—a profile that is consistent with dynamic aphasia. By providing a brief review of pertinent literature and the results from our neurologic, speech and language, neuropsychological, and neuroimaging testing, this report sheds light on the infrequently reported dynamic aphasia in the context of frontotemporal dementia. Our patients’ insights into their verbal difficulty tend to support the notion that dynamic aphasia results from interference at the stage where thoughts are converted into verbal messages—that is, the thought–verbal interface.
Effectiveness and durability of protection against future SARS-CoV-2 infection conferred by COVID-19 vaccination and previous infection; findings from the UK SIREN prospective cohort study of healthcare workers March 2020 to September 2021
Authors: Hall Victoria , Foulkes Sarah , Insalata Ferdinando , Saei Ayoub , Kirwan Peter , Atti Ana , Wellington Edgar , Khawam Jameel , Munro Katie , Cole Michelle , Tranquillini Caio , Taylor-Kerr Andrew , Hettiarachchi Nipunadi , Calbraith Davina , Sajedi Noshin , Milligan Iain , Themistocleous Yrene , Corrigan Diane , Cromey Lisa , Price Lesley , Stewart Sally , de Lacy Elen , Norman Chris , Linley Ezra , Otter Ashley David , Semper Amanda , Hewson Jacqueline , D’Arcangelo Silvia ,   the SIREN Study Group, Chand Meera , Brown Colin S , Brooks Tim , Islam Jasmin , Charlett Andre , Hopkins Susan
Published: December 2021

Background

Understanding the duration and effectiveness of infection and vaccine-acquired SARS-CoV-2 immunity is essential to inform pandemic policy interventions, including the timing of vaccine-boosters. We investigated this in our large prospective cohort of UK healthcare workers undergoing routine asymptomatic PCR testing.

Methods

We assessed vaccine effectiveness (VE) (up to 10-months after first dose) and infection-acquired immunity by comparing time to PCR-confirmed infection in vaccinated and unvaccinated individuals using a Cox regression-model, adjusted by prior SARS-CoV-2 infection status, vaccine-manufacturer/dosing-interval, demographics and workplace exposures.

Results

Of 35,768 participants, 27% (n=9,488) had a prior SARS-CoV-2 infection. Vaccine coverage was high: 97% had two-doses (79% BNT162b2 long-interval, 8% BNT162b2 short-interval, 8% ChAdOx1). There were 2,747 primary infections and 210 reinfections between 07/12/2020 and 21/09/2021. Adjusted VE (aVE) decreased from 81% (95% CI 68%-89%) 14-73 days after dose-2 to 46% (95% CI 22%-63%) >6-months; with no significant difference for short-interval BNT162b2 but significantly lower aVE (50% (95% CI 18%-70%) 14-73 days after dose-2 from ChAdOx1. Protection from infection-acquired immunity showed evidence of waning in unvaccinated follow-up but remained consistently over 90% in those who received two doses of vaccine, even in those infected over 15-months ago.

Conclusion

Two doses of BNT162b2 vaccination induce high short-term protection to SARS-CoV-2 infection, which wanes significantly after six months. Infection-acquired immunity boosted with vaccination remains high over a year after infection. Boosters will be essential to maintain protection in vaccinees who have not had primary infection to reduce infection and transmission in this population.

Trial registration number

ISRCTN11041050