bluuebunny/crossref_metadata_2025 huggingface dataset:
O79: THE ROLE OF SENTINEL LYMPH NODE BIOPSY IN BREAST CANCER PATIENTS OVER THE AGE OF 80 – HOW MUCH IS ENOUGH?
Authors: Doyle S , Hanley G , Boland MR , Balasubramanian I , McCartan D , Geraghty J , Evoy D , Prichard RS , McDermott EW ,   St. Vincent's University Hospital
Published: April 2021

Introduction

Recent studies have suggested that sentinel lymph node biopsy (SLNB) can be omitted in newly diagnosed elderly breast cancer (BC) patients as it may not influence decisions regarding further therapeutic intervention. The aim of this study was to assess the impact of SLNB on further surgical intervention as well as adjuvant treatments in patients over the age of 80.

Method

A retrospective study was performed involving all BC patients over the age of 80 diagnosed between 2008 and 2017 who underwent SLNB as part of their initial surgery. Patient/tumour characteristics and adjuvant treatments were recorded.

Result

127 patients underwent SLNB in the study period. The median age was 82 (Range: 80-95). 91/127 (71.6%) had ductal pathology, median tumour grade was 2, and oestrogen receptor positivity was seen in 89% of patients. The median number of sentinel nodes removed was 2 (Range: 1-6). 45 patients (35.4%) had a positive sentinel node (median positive nodes = 1). Of the 45 patients, 11 proceeded to axillary lymph node dissection (ALND) (11/127; 8.6%). The median number of nodes excised during ALND was 14 (Range:7-25) and 6 patients (6/11) had further positive nodes. 9% of patients with a positive node received adjuvant chemotherapy, 87% received adjuvant radiotherapy and 79% received hormonal therapy.

Conclusion

Although SLNB positivity is still used in the elderly patients, only a few patients (<10%) proceed to ALND or receive adjuvant chemotherapy. Hence performing a SLNB should be carefully considered when treating patients over the age of 80

Take-home message

The use of SLNB in elderly patients needs to be considered in node negative patients
P2: CONSIDERATIONS IN SURGICAL VERSUS NONSURGICAL MANAGEMENT OF HEAD AND NECK MERKEL CELL CARCINOMA
Authors: Crotty T , McHugh A , Griffith P , Moran T
Published: April 2021

Introduction

MCC is a rare cutaneous neuroendocrine tumour with a high risk of regional and distant metastasis. Management of this highly aggressive tumour is complex and mandates a multidisciplinary approach for optimal outcomes.

Method

Over 12 months, three cases of MCC in the cervicofacial region were identified and described. A critical review of the literature is included.

Result

Tumour staging confirmed 2/3 cases had regional spread. One patient underwent unilateral parotidectomy with modified radical neck dissection and adjuvant radiotherapy. The other case is awaiting radiotherapy following a selective neck dissection. The final case had no further surgery and is currently under surveillance.

Conclusion

This case series illustrates the diversity in managing cervicofacial MCC's at various stages of their development.

Take-home message

Merkel cell carcinoma must be managed aggressively with a multidisciplinary approach, regardless of how localised it may appear.
P3: CASE-CONTROL STUDY OF SEXUAL BEHAVIOUR IN HPV-POSITIVE ORAL CAVITY AND OROPHARYNGEAL CANCER
Authors: Crotty T , Brennan S , Cousins G , Kinsella J , Moran T
Published: April 2021

Introduction

HPV infection is recognised as the main aetiological factor responsible for the increased incidence of oropharyngeal squamous cell carcinomas (OPSCC). Currently the epidemiology of oral HPV infection and OPSCC is poorly understood. In this study we aim to define the relationship between sexual behaviours and HPV-positive OPSCC.

Method

We performed a hospital-based, case-control study of 30 patients with HPV-positive and 30 patients with HPV-negative newly diagnosed oral cavity and OPSCC. The participants underwent questionnaire based interviews investigating variables such as age, gender, tobacco use, alcohol intake, and sexual behaviour.

Result

Subjects in the HPV-positive tumour subgroup had significantly less tobacco use then their HPV-negative counterparts (odds ratio, 0.92, 95% CI 0.9-1.17). A history of oral sexual activity was significantly more likely in the HPV-positive tumour subgroup (odds ratio, 5.23, 95% CI, 1.66-16.51), however this association did not remain significant when adjusted for age, gender, smoking and alcohol consumption. Similarly, there was significantly less alcohol consumption overall in the HPV-positive tumour subgroup (odds ratio, 0.107, 95% CI 0.96-1.01), but this association was no longer significant when adjusted for covariables.

Conclusion

Significantly less smoking was prevalent in patients with HPV-positive OPSCC. Although patients with HPV-positive tumours had less alcohol consumption and a stronger history of oral sexual activity overall, greater numbers are required in order to show a significant association. This further supports the known association between HPV-infection and OPSCC and the department of health's decision to commence vaccination of boys before the onset of sexual activity.

Take-home message

HPV-positive oropharyngeal cancer can develop without exposure to established risk factors such as tobacco use or excessive alcohol consumption. This change in pathogenesis should lead a change in how we prevent and manage the disease.
P12: PREDICTORS OF CONVERSION FROM MINIMALLY INVASIVE TO OPEN ADRENALECTOMY: A SYSTEMATIC REVIEW & META-ANALYSIS OF OBSERVATIONAL STUDIES
Authors: Cagney D , O'Leary DP , Razzaq Z , Majeed M , Redmond HP
Published: April 2021

Introduction

Minimally invasive adrenalectomy has become the standard of care internationally in benign adrenal disease. Intra-operative conversion to open surgery is associated with significantly increased morbidity and prolonged hospital stay. The aim of this systematic review is to identify risk factors associated with intra-operative conversion of minimally invasive adrenalectomy.

Method

This systematic review was conducted according to MOOSE guidelines. PubMed, EMBASE and Cochrane library were systematically searched for observational studies evaluating risk factors for intra-operative conversion of minimally invasive adrenalectomy to open surgery. Specific risk factors of interest included patient demographics, patient co-morbidities, tumour characteristics and histology.

Result

Eight studies met the inclusion criteria for analysis with a total of 2939 patients. 6.02% (n=177) required intra-operative conversion. 67.5% (n=1983) underwent laparoscopic transperitoneal adrenalectomy. There were no significant associations between any patient demographics or co-morbidities and intra-operative conversion. Tumour characteristics such as right sided tumours (pooled odds ratio (OR), 1.51; 95% Confidence Interval (CI), 0.98-2.32; p=0.06) and increasing tumour size (OR, 2.29; 95% CI, 1.4-3.74; p=0.001) were shown to be significantly associated with an increased risk of conversion. Pheochromocytoma (OR, 2.21; 95% CI, 1.89-2.58; p<0.0001) and malignancy (OR, 5.38; 95% CI, 2.1-13.81; p=0.005) were also significant predictors of intra-operative conversion.

Conclusion

Minimally invasive adrenalectomy has significantly reduced post-operative morbidity in patients requiring adrenal surgery but the need for intra-operative conversion remains significant. Identifying patients at increased risk of conversion pre-operatively may assist intra-operative decision making and contribute to improved patient outcomes.

Take-home message

Minimally invasive adrenalectomy carries a significant risk of conversion. Recognising patients with known risk factors for conversion aids risk stratification and may contribute to better outcomes.
P14: DISCONTINUATION AND NON-PUBLICATION OF SURGICAL RANDOMISED CONTROLLED TRIALS IN THE SETTING OF ILEUS: OBSERVATIONAL STUDY
Authors: Helliwell JA , Chapman SJ , Jayne DG
Published: April 2021

Introduction

Once regarded as an inevitable occurrence after surgery, ileus is now recognised as an unmet clinical need. Despite this, few studies have shown meaningful clinical benefit which may be due to the challenges associated with conducting trials in this setting. The aim of this study was to determine the rate of discontinuation and non-publication of randomised controlled trials (RCTs) in the setting of ileus.

Method

A systematic search of ClinicalTrials.gov was performed using the keyword “ileus”. RCTs registered between 2003-2019 involving abdominal surgery were eligible. Studies were divided according to completion status. Authors were contacted to seek information about the circumstances for discontinuation and non-publication. For completed studies, evidence of a published manuscript was sought.

Result

Of 262 trials identified, 81 were eligible for analysis. Amongst 27 discontinued trials, email addresses were identified for 24 (88.9%) and replies received from 6 (25.1%). The most common reasons for discontinuation were loss of clinical significance (n=2) and insufficient recruitment (n=2). Amongst 54 completed studies, manuscripts were identified for 34 (63.0%). Of these, email addresses were identified for 12 (60.0%) and replies received from 5 (41.7%). The most common reason for non-publication was a lack of time/resources/personnel (n=3).

Conclusion

One third of trials undertaken were discontinued and of those which did reach completion, less than two thirds reported results. A lack of resources and loss of clinical significance were predominant reasons. There is an urgent need to address methodological barriers in research relating to ileus to promote rigorous evaluation of new treatments.

Take-home message

One third of trials undertaken were discontinued and of those which did reach completion, less than two thirds reported results. A lack of resources and loss of clinical significance were predominant reasons. There is an urgent need to address methodological barriers in research relating to ileus to promote rigorous evaluation of new treatments.
P17: IMPROVING PLASTIC SURGERY OPERATION NOTE ACCESSABILITY AT A MAJOR TRAUMA CENTRE: A PROSPECTIVE COMPLETED AUDIT CYCLE
Authors: Geoghegan L , Reissis D
Published: April 2021

Introduction

Quality operation note documentation is essential for ensuring continuity of care amongst the multi-disciplinary team. The Royal College of Surgeons has published clear and succinct guidelines which outline the necessity for timely, accurate and accessible operation note documentation. Our department uses a bespoke electronic operation note template which is stored within a departmental database. The aim of this study was to evaluate the effect of online operation note guidance on the accessibility of operative documentation.

Method

A prospective audit of operation note documentation was conducted during two one-month periods in May and November 2018. All reconstructive surgical procedures, both trauma and elective, were included. A bespoke online reminder system was introduced to our electronic platform to encourage operation note upload onto electronic medical records.

Result

224 cases (127 elective, 98 consultant-led) were included in the initial audit and 239 cases (173 elective, 131 consultant-led) in the post-intervention audit. 56% of operation notes were accessible to nursing staff pre-intervention. Post-intervention 83% of operation notes were accessible to nursing staff (p< 0.05). No significant correlation was found between operation note accessibility and the type of case (elective vs emergency, r= -0.179), grade of operating surgeon (consultant vs registrar, r=0.259) and the number of operating surgeons (r=0.208).

Conclusion

This study highlights the importance of operation note accessibility to every member of the multidisciplinary team. A pop-up based intervention significantly improved accessibility of operation notes within electronic medical records although performance remains significantly below the expected standard.

Take-home message

The use of bespoke, online platforms may limit access to operation notes. A simple, pop-up based intervention significantly improves upload rate to electronic medical records however accessibility remains significantly below the expected standard.
P18: CONVENTIONAL DUPUYTREN'S DIATHESIS FACTORS ARE NOT ASSOCIATED WITH POOR OUTCOME FOLLOWING SURGERY: A SYSTEMATIC REVIEW
Authors: Geoghegan L , Man J , Jain A , Rodrigues JN
Published: April 2021

Introduction

Dupuytren's diathesis describes an aggressive disease course with tendency for recurrence or extension following intervention. Conventional factors associated with Dupuytren's diathesis are ethnicity, family history, bilateral and ectopic disease. Disease recurrence is not the only cause of poor outcome following intervention. This systematic review aimed to identify all factors that have been investigated for a potential association with the development, progression, recurrence and outcome of treatment in Dupuytren's diathesis.

Method

A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Abstract screening and data extraction were performed in duplicate. Included prognostic cohort studies were quality assessed using the Quality in Prognosis Study tool.

Result

The search revealed 2,661 records from which 11 full text articles reported both conventional diathesis factors and outcomes (in addition to recurrence) following intervention for Dupuytren's in 938 patients. Collectively 67% underwent fasciectomy and seven outcomes were reported: three patient reported outcome measures (DASH, quick-DASH and EQ-5D), three functional measures (grip strength, joint angle correction and range of motion) and treatment complications. Two studies used multiple univariate statistical techniques and found no significant association between diathesis factors and disease outcome.

Conclusion

This systematic review challenges conventional notions of Diathesis factors and provides a comprehensive appraisal of factors associated with poor outcome following intervention for Dupuytren's disease.

Take-home message

Conventional factors associated with recurrence in Dupuytren's disease are not associated with poor outcome following intervention.
P19: THE RELIABILITY OF VENOUS THROMBOEMBOLISM RISK ASSESSMENT TOOLS FOLLOWING FREE FLAP RECONSTRUCTION OF THE LOWER EXTREMITIES
Authors: Geoghegan L , Super J , Onida S , Hettiaratchy S , Davies A
Published: April 2021

Introduction

The incidence of flap failure in lower extremity reconstruction is significantly higher in the lower extremity compared head, neck and breast reconstruction. The commonest cause of flap failure is venous thrombosis. The aim of this study was to assess the reliability of VTE risk assessment tools in patients with open lower extremity fractures and to assess the ability of such tools to identify patients at risk of developing microvascular venous thrombosis following lower extremity free flap reconstruction.

Method

A single centre retrospective cohort study was conducted between August 2012-August 2019. All patients were risk assessed using the Department of Health (DoH), Modified Caprini and Padua VTE risk assessment tools.

Result

58 patients were included, all were at high risk of DVT according to the DoH (mean score± SD, 3.7±0.93), Caprini (10.2±1.64) and Padua (5.4±0.86) risk assessment tools. All patients received thromboprophylaxis, the incidence of clinical deep venous thrombosis was 0%. Intraclass correlation coefficient demonstrated moderate agreement between the Caprini and DoH (0.73, 95% CI 0.54-0.84, p<0.001), the Caprini and Padua (0.52, 95% CI 0.19-0.72, p<0.001) and the DoH and Padua (0.74, 95% CI 0.57-0.85, p<0.001). Microvascular venous thrombosis occurred in 6 patients, resulting in 2 amputations. There were no significant differences in scores between those with and without venous complications.

Conclusion

Current VTE risk assessment tools do not identify patients at risk of developing venous complications following lower extremity reconstruction. Further prospective studies are required to optimise risk prediction models and thromboprophylaxis use in this cohort.

Take-home message

Current VTE risk assessment tools do not identify patients at risk of developing microvascular venous thrombosis following lower limb reconstruction.
P24: MANAGEMENT OF RHEUMATIC VALVE DISEASE OF THE AORTIC VALVE USING THE OZAKI PROCEDURE WITH AUTOLOGOUS PERICARDIUM
Authors: Asif A , Caputo M
Published: April 2021

Case-Study

A 15-year-old boy was referred to our tertiary centre from his local paediatric services with a background of rheumatic fever, severe aortic regurgitation (AR) and mild to moderate mitral regurgitation. He had a history of angina and dyspnoea on exertion, a 2/6 ejection systolic murmur and 2/4 end diastolic murmur. Transthoracic echocardiography showed severe aortic valve insufficiency (with flow reversal seen in the descending aorta and an LV end diastolic volume of 173 ml/m2) and trivial pulmonary valve regurgitation. Autograft failure following the favoured Ross procedure deemed the patient as a candidate for an Ozaki procedure. Autologous pericardium was used to replace the diseased aortic valve. Intraoperative transoesophageal echocardiography showed a deficient left coronary cusp leaflet and a retracted right coronary cusp leaflet. The patient was under cardiopulmonary bypass for 124 minutes and on cross-clamping for 99 minutes with no intraoperative complications. Histological examination of the aortic valve leaflets showed neovascularisation, myxoid changes and disarray of the fibrous stroma. Postoperative recovery was uneventful. The postoperative echocardiogram showed trivial AR, end diastolic volume 217ml, end systolic volume 12 ml and 40% ejection fraction. There was full resolution of the dyspnoea, angina and diastolic murmur on follow-up 4-months postoperatively as supported by healthy valve function on echocardiography. This case highlights that in those of risk of multiple valve pathology, such as in rheumatic valve disease, an Ozaki procedure using autologous pericardium is a viable surgical option for paediatric aortic valve repair with good outcomes.

Take-home message

In cases of systemic conditions affecting the heart valves where there is multiple valve pathology and risk of autograft failure, such as rheumatic valve disease, the use of autologous pericardium to replace these valves has shown to be a viable option in this paediatric case.
P25: EVALUATING THE JOINT EFFECT OF BODY MASS INDEX AND DIABETES WITH LATE-MORTALITY AFTER CORONARY ARTERY BYPASS GRAFTING
Authors: Asif A , Rayner T , Bruno VD , Benedetto U
Published: April 2021

Introduction

Survival analyses following coronary artery bypass grafting (CABG) evaluate the independent effects of body mass index (BMI) and diabetes. However, BMI and diabetes are correlated and their combined effects should be considered, thus we examined the joint association on long-term survival after CABG.

Method

A total of 15129 patients undergoing isolated CABG between 1997 and 2017 were analysed. The BMI categories were defined as Normal-Weight (≥18-<25 kg/m2;n=3783), Overweight (≥25-<30 kg/m2;n=7103), Class-I-Obese (≥30-<35kg/m2;n=3247), and Class-II-Obese (≥35 kg/m2;n=996). Diabetes was defined as ever having a diagnosis of diabetes (n=3203). The association was assessed using Cox-proportional hazards regression models.

Result

During follow-up, 3140 deaths occurred. Compared to Normal-Weight individuals, the multivariable-adjusted hazard ratios (HR) were 0.89 [95%CI: 0.82-0.96], 0.95 [95%CI: 0.86-1.10], and 1.30 [95%CI: 1.07-1.47] for Overweight, Class-I-Obese, and Class-II-Obese patients, respectively. Compared to non-diabetic patients, the multivariable-adjusted HR for diabetic patients was 1.55 [95%CI: 1.43-1.68]. In the joint analysis, compared to Normal-Weight non-diabetic individuals, the multivariable-adjusted HRs were: Normal-Weight diabetic 1.30 [95%CI: 1.10-1.53], Overweight non-diabetic 0.86 [95%CI: 0.78-0.94], Overweight diabetic 1.32 [95%CI: 1.16-1.50], Class-I-Obese non-diabetic 0.87 [95%CI: 0.77-0.99], Class-I-Obese diabetic 1.58 [95%CI: 1.53-1.85], Class-II-Obese non-diabetic 1.11 [95%CI: 0.90-1.38], and Class-II-Obese diabetic 2.06 [95%CI: 1.65-2.56]. The reduction in multivariable-adjusted 10-year survival rates for diabetics versus non-diabetics was 4%, 6%, 9%, and 14% for Normal-Weight, Overweight, Class-I-Obese, and Class-II-Obese, respectively.

Conclusion

A considerable difference in survival after CABG is seen in the joint analysis of diabetes and BMI and should therefore be considered in future studies.

Take-home message

Diabetes and body mass index (BMI) are both correlated with the incidence of coronary artery disease and the need for coronary artery bypass grafting (CABG) and are often statistically analysed as separate entities. We show that the joint affect of diabetes and BMI has a significantly higher risk of late-mortality following CABG, therefore such analyses should be considered in future studies.
P26: EVALUATING AND DEVELOPING A TEACHING TOOL ON FAECAL INCONTINENCE IN THE UNDERGRADUATE MEDICAL CURRICULUM
Authors: Li CH , Parker J , Reeve N , Cornish J
Published: April 2021

Introduction

To evaluate the medical school undergraduate curriculum on faecal incontinence (FI) and develop an educational tool to improve the teaching on the subject.

Method

Qualitative analysis of literature research and data collected from medical students via emails, questionnaires and focused group discussions.

Result

FI has not been implanted into the undergraduate curriculum 12,13 and there are variations in teaching on the topic in different medical schools. n= 111 medical students at Cardiff University responded to the survey. FI was reported to be overlooked compared to other types of bowel dysfunction. 38 students reported to have teaching on bowel incontinence, whereas 64 and 74 students had teaching on diarrhoea and constipation respectively. 77% of medical students would like more teaching on bowel incontinence. 9 students participated in a focused group discussion. An interactive e-learning module from Xerte was created based on the students' suggestions and were trialed by a separate cohort of students (n=20). All 20 students showed significant improvement of students' confidence in faecal incontinence (p <= 2.132e∧-6) after completing the e-learning module.

Conclusion

We recommend introducing the educational resource into the undergraduate curriculum of Cardiff University medical school, especially targeting the clinical year, a clear guidance for FI should be published by the relevant postgraduate healthcare faculties and consider assessing at which stage of the postgraduate training should FI be taught.

Take-home message

Baseline knowledge of FI is poor. Lack of content in medical school curriculum and E learning modules potentially useful adjuncts.
Premarket Development Times for Innovative Vaccines––To What Extent Are the Coronavirus Disease 2019 (COVID-19) Vaccines Outliers?
Authors: Beall Reed F , Kesselheim Aaron S , Hollis Aidan
Published: April 2021

One reason expressed in surveys of people reporting coronavirus disease 2019 (COVID-19) vaccine hesitancy is how rapidly these vaccines have reached the market. To estimate the length of time the COVID-19 vaccine spent in research and development as compared to other novel vaccines, we apply previously established methods for estimating medical product development times, using the key associated patent filings cited by the manufacturer as the marker of when commercial development activity began. Applying these methods to a cohort of recently approved innovative vaccines and comparing them to the first-approved COVID-19 vaccine (BioNTech/Pfizer), we found key patent filings for the technology in this COVID-19 vaccine occurred 10.0 years prior to regulatory authorization. By this metric, the development timelines for innovative vaccines have been shortening since the 1980s, and the COVID-19 vaccine comfortably fits within this pattern. Vaccine development timelines have now even drawn to parity with many of the most commonly used drugs.
Air Pollution and Manufacturing Firm Productivity: Nationwide Estimates for China
Authors: Fu Shihe , Viard V Brian , Zhang Peng
Published: April 2021

We provide nationwide causal estimates of air pollution's effect on short-run productivity for China's manufacturing sector from 1998 to 2007. Using thermal inversions as an instrument, a 1 µg/m3 decrease in PM2.5 increases productivity by 0.82% (elasticity of −0.44). Increased hiring attenuates the elasticity to −0.17. Differential effects of a trade shock on coastal versus inner regions imply a pollution elasticity of output of 1.43. Simulating a dynamic general-equilibrium model yields an output elasticity of −0.28 with respect to PM2.5. An exogenous 1% decrease in PM2.5 nationwide increases gross domestic product by 0.039%.
A New Statistic for Detecting Genetic Differentiation
Authors: Hudson Richard R
Published: April 2021

A new statistic for detecting genetic differentiation of subpopulations is described. The statistic can be calculated when genetic data are collected on individuals sampled from two or more localities. It is assumed that haplotypic data are obtained, either in the form of DNA sequences or data on many tightly linked markers. Using a symmetric island model, and assuming an infinite-sites model of mutation, it is found that the new statistic is as powerful or more powerful than previously proposed statistics for a wide range of parameter values.
Continuous Exchange of Sequence Information Between Dispersed Tc1 Transposons in the Caenorhabditis elegans Genome
Authors: Fischer Sylvia E J , Wienholds Erno , Plasterk Ronald H A
Published: April 2021

In a genome-wide analysis of the active transposons in Caenorhabditis elegans we determined the localization and sequence of all copies of each of the six active transposon families. Most copies of the most active transposons, Tc1 and Tc3, are intact but individually have a unique sequence, because of unique patterns of single-nucleotide polymorphisms. The sequence of each of the 32 Tc1 elements is invariant in the C. elegans strain N2, which has no germline transposition. However, at the same 32 Tc1 loci in strains with germline transposition, Tc1 elements can acquire the sequence of Tc1 elements elsewhere in the N2 genome or a chimeric sequence derived from two dispersed Tc1 elements. We hypothesize that during double-strand-break repair after Tc1 excision, the template for repair can switch from the Tc1 element on the sister chromatid or homologous chromosome to a Tc1 copy elsewhere in the genome. Thus, the population of active transposable elements in C. elegans is highly dynamic because of a continuous exchange of sequence information between individual copies, potentially allowing a higher evolution rate than that found in endogenous genes.
Mitochondrial Genotype Affects Fitness inDrosophila simulans
Authors: James Avis C , Ballard J William O
Published: April 2021

Drosophila simulans is known to harbor three distinct mitochondrial DNA (mtDNA) haplotype groups (siI, -II, and -III) with nearly 3.0% interhaplotypic divergence but <0.06% intrahaplotypic diversity. With the large amount of genetic variation in this system, the potential power to detect intraspecific fitness differences in fly lines that carry distinct haplotypes is great. We test three life-history traits on fly lines with known sequence differences in the mtDNA genome after controlling the nuclear genome by backcrossing. We find that flies with the siI haplotype are fastest developing and have the lowest probability of surviving to three experimental periods (2–6, 12–17, and 34–39 days of age). Wild-type males with siIII mtDNA were more active while disruption of specific coadapted nucleo-mitochondrial complexes caused a significant decrease in activity. These results are discussed in the context of the geographic distribution of each haplotype.
Genetic Diversity and Population History of Golden Monkeys (Rhinopithecus roxellana)
Authors: Li Haipeng , Meng Shi-Jie , Men Zheng-Ming , Fu Yun-Xin , Zhang Ya-Ping
Published: April 2021

Golden monkey (Rhinopithecus roxellana), namely the snub-nosed monkey, is a well-known endangered primate, which distributes only in the central part of mainland China. As an effort to understand the current genetic status as well as population history of this species, we collected a sample of 32 individuals from four different regions, which cover the major habitat of this species. Forty-four allozyme loci were surveyed in our study by allozyme electrophoresis, none of which was found to be polymorphic. The void of polymorphism compared with that of other nonhuman primates is surprising particularly considering that the current population size is many times larger than that of some other endangered species. Since many independent loci are surveyed in this study, the most plausible explanation for our observation is that the population has experienced a recent bottleneck. We used a coalescent approach to explore various scenarios of population bottleneck and concluded that the most recent bottleneck could have happened within the last 15,000 years. Moreover, the proposed simulation approach could be useful to researchers who need to analyze the non- or low-polymorphism data.
Cloning and Characterization of Maize B Chromosome Sequences Derived From Microdissection
Authors: Cheng Ya-Ming , Lin Bor-Yaw
Published: April 2021

Isolation of sequences from the maize B chromosome is always hampered by its high homology with the normal complements. In this study, this handicap was overcome by cloning the sequences from the pachytene B chromosomes dissected out of a slide by a micromanipulator followed by degenerate oligonucleotide-primed PCR. The isolated sequences were found to hybridize with genomic DNA in a B-dosage-dependent manner and with the pachytene B chromosome by fluorescence in situ hybridization (FISH), corroborating their B origin. A total of 19 B sequences were isolated, all of which are repetitive and, with one exception, are homologous to the A chromosome(s). Three sequences have strong homology to maize sequences that include two knob repeats and one zein gene (noncoding region), and 10 others are homologous to the noncoding region of Adh1, Bz1, Gag, Zein, and B centromere to a lesser degree. Six sequences have no homology to any gene. In addition to FISH, the B-specific sequence and a partially B-specific one were also mapped, by seven newly characterized TB-10L translocations, to a similar location on the central portion of the distal heterochromatic region, spreading over a region of about one-third of the B chromosome.
Positive and Negative Roles of Homologous Recombination in the Maintenance of Genome Stability in Saccharomyces cerevisiae
Authors: Yoshida Jumpei , Umezu Keiko , Maki Hisaji
Published: April 2021

In previous studies of the loss of heterozygosity (LOH), we analyzed a hemizygous URA3 marker on chromosome III in S. cerevisiae and showed that homologous recombination is involved in processes that lead to LOH in multiple ways, including allelic recombination, chromosome size alterations, and chromosome loss. To investigate the role of homologous recombination more precisely, we examined LOH events in rad50Δ, rad51Δ, rad52Δ, rad50Δ rad52Δ, and rad51Δ rad52Δ mutants. As compared to Rad+ cells, the frequency of LOH was significantly increased in all mutants, and most events were chromosome loss. Other LOH events were differentially affected in each mutant: the frequencies of all types of recombination were decreased in rad52 mutants and enhanced in rad50 mutants. The rad51 mutation increased the frequency of ectopic but not allelic recombination. Both the rad52 and rad51 mutations increased the frequency of intragenic point mutations ∼25-fold, suggesting that alternative mutagenic pathways partially substitute for homologous recombination. Overall, these results indicate that all of the genes are required for chromosome maintenance and that they most likely function in homologous recombination between sister chromatids. In contrast, other recombination pathways can occur at a substantial level even in the absence of one of the genes and contribute to generating various chromosome rearrangements.
Molecular Characterization and Analysis of the acrB Gene of Aspergillus nidulans: A Gene Identified by Genetic Interaction As a Component of the Regulatory Network That Includes the CreB Deubiquitination Enzyme
Authors: Boase Natasha A , Lockington Robin A , Adams Julian R J , Rodbourn Louise , Kelly Joan M
Published: April 2021

Mutations in the acrB gene, which were originally selected through their resistance to acriflavine, also result in reduced growth on a range of sole carbon sources, including fructose, cellobiose, raffinose, and starch, and reduced utilization of ω-amino acids, including GABA and β-alanine, as sole carbon and nitrogen sources. The acrB2 mutation suppresses the phenotypic effects of mutations in the creB gene that encodes a regulatory deubiquitinating enzyme, and in the creC gene that encodes a WD40-repeat-containing protein. Thus AcrB interacts with a regulatory network controlling carbon source utilization that involves ubiquitination and deubiquitination. The acrB gene was cloned and physically analyzed, and it encodes a novel protein that contains three putative transmembrane domains and a coiled-coil region. AcrB may play a role in the ubiquitination aspect of this regulatory network.
Repair of Damaged and Mismatched DNA by the XPC Homologues Rhp41 and Rhp42 of Fission Yeast
Authors: Marti Thomas M , Kunz Christophe , Fleck Oliver
Published: April 2021

Rhp41 and Rhp42 of Schizosaccharomyces pombe are homologues of human XPC, which is involved in nucleotide excision repair (NER) of damaged DNA. Inactivation of rhp41 caused moderate sensitivity to ultraviolet (UV) radiation. In addition, an increase of mitotic mutation rates was observed in the rhp41 mutant, which was dependent on active translesion polymerase Z. UV sensitivity and mutation rates were not different between rhp42 and wild type, but compared to rhp41 were further increased in rhp41 rhp42 cells. Transcription of the fbp1 gene (induced in vegetative cells) and of the SPBC1289.14 gene (induced during meiosis) was strongly blocked by UV-induced damages in the rhp41 mutant, but not, or only slightly, reduced in rhp42 background. NER-dependent short-patch repair of mismatches formed during meiosis was slightly affected in rhp41, moderately affected in rhp42, and absent in rhp41 rhp42. Epistasis analysis with rhp7 and rhp26 indicates that Rhp41 and Rhp42 are both involved in the global genome and transcription-coupled repair subpathways of NER. Rhp41 plays a major role in damage repair and Rhp42 in mismatch repair.
The G-Protein α-Subunit GasC Plays a Major Role in Germination in the Dimorphic FungusPenicillium marneffei
Authors: Zuber Sophie , Hynes Michael J , Andrianopoulos Alex
Published: April 2021

The opportunistic human pathogen Penicillium marneffei exhibits a temperature-dependent dimorphic switch. At 25°, multinucleate, septate hyphae that can undergo differentiation to produce asexual spores (conidia) are produced. At 37° hyphae undergo arthroconidiation to produce uninucleate yeast cells that divide by fission. This work describes the cloning of the P. marneffei gasC gene encoding a G-protein α-subunit that shows high homology to members of the class III fungal Gα-subunits. Characterization of a ΔgasC mutant and strains carrying a dominant-activating gasCG45R or a dominant-interfering gasCG207R allele show that GasC is a crucial regulator of germination. A ΔgasC mutant is severely delayed in germination, whereas strains carrying a dominant-activating gasCG45R allele show a significantly accelerated germination rate. Additionally, GasC signaling positively affects the production of the red pigment by P. marneffei at 25° and negatively affects the onset of conidiation and the conidial yield, showing that GasC function overlaps with functions of the previously described Gα-subunit GasA. In contrast to the S. cerevisiae ortholog Gpa2, our data indicate that GasC is not involved in carbon or nitrogen source sensing and plays no major role in either hyphal or yeast growth or in the switch between these two forms.
Dynamics of Molecular Markers Linked to the Resistance Loci in a Mosquito-Plasmodium System
Authors: Yan Guiyun , Severson David W
Published: April 2021

Models on the evolution of resistance to parasitism generally assume fitness tradeoffs between the costs of being parasitized and the costs associated with resistance. This study tested this assumption using the yellow fever mosquito Aedes aegypti and malaria parasite Plasmodium gallinaceum system. Experimental mosquito populations were created by mixing susceptible and resistant strains in equal proportions, and then the dynamics of markers linked to loci for Plasmodium resistance and other unlinked neutral markers were determined over 12 generations. We found that when the mixed population was maintained under parasite-free conditions, the frequencies of alleles specific to the susceptible strain at markers closely linked to the loci for resistance (QTL markers) as well as other unlinked markers increased significantly in the first generation and then fluctuated around equilibrium frequencies for all six markers. However, when the mixed population was exposed to an infected blood meal every generation, allele frequencies at the QTL markers for resistance were not significantly changed. Small population size caused significant random fluctuations of allele frequencies at all marker loci. Consistent allele frequency changes in the QTL markers and other unlinked markers suggest that the reduced fitness in the resistant population has a genome-wide effect on the genetic makeup of the mixed population. Continuous exposure to parasites promoted the maintenance of alleles from the resistant Moyo-R strain in the mixed population. The results are discussed in relation to the proposed malaria control strategy through genetic disruption of vector competence.
Cytoplasmic Incompatibility and Sperm Cyst Infection in Different Drosophila-Wolbachia Associations
Authors: Veneti Zoe , Clark Michael E , Zabalou Sofia , Karr Timothy L , Savakis Charalambos , Bourtzis Kostas
Published: April 2021

Wolbachia are a group of maternally transmitted obligatory intracellular α-proteobacteria that infect a wide range of arthropod and nematode species. Wolbachia infection in Drosophila in most cases is associated with the induction of cytoplasmic incompatibility (CI), manifested as embryonic lethality of offspring in a cross between infected males and uninfected females. While the molecular basis of CI is still unknown, it has been suggested that two bacterial functions are involved: mod (for modification) modifies the sperm during spermatogenesis and resc (for rescue) acts in the female germline and/or in early embryos, neutralizing the modification. There is considerable variation in the level of incompatibility in different Wolbachia/host interactions. We examine the relationship between the levels of CI in a number of naturally infected and transinfected Drosophila hosts and the percentage of Wolbachia-infected sperm cysts. Our results indicate the presence of two main groups of Drosophila-Wolbachia associations: group I, which exhibits a positive correlation between CI levels and the percentage of infected sperm cysts (mod+ phenotype), and group II, which does not express CI (mod– phenotype) irrespective of the infection status of the sperm cysts. Group II can be further divided into two subgroups: The first one contains associations with high numbers of heavily Wolbachia-infected sperm cysts while in the second one, Wolbachia is rarely detected in sperm cysts, being mostly present in somatic cells. We conclude that there are three requirements for the expression of CI in a host-Wolbachia association: (a) Wolbachia has to be able to modify sperm (mod+ genotype), (b) Wolbachia has to infect sperm cysts, and (c) Wolbachia has to be harbored by a permissive host.
Distinct Phospholipase C-γ-Dependent Signaling Pathways in the Drosophila Eye and Wing Are Revealed by a New small wing Allele
Authors: Mankidy Rishikesh , Hastings Jeremy , Thackeray Justin R
Published: April 2021

The Drosophila genome contains a single phospholipase C-γ (PLC-γ) homolog, encoded by small wing (sl), that acts as an inhibitor of receptor tyrosine kinase (RTK) signaling during photoreceptor R7 development. Although the existing sl alleles behave genetically as nulls, they may still produce truncated Sl products that could in theory still provide limited PLC-γ function. Both to identify a true null allele and to probe structure-function relationships in Sl, we carried out an F1 screen for new sl mutations and identified seven new alleles. Flies homozygous for any of these alleles are viable, with the same short-wing phenotype described previously; however, two of the alleles differ from any of those previously isolated in the severity of the eye phenotype: sl9 homozygotes have a slightly more extreme extra-R7 phenotype, whereas sl7 homozygotes have an almost wild-type eye. We determined the mutant defect in all seven alleles, revealing that sl9 is a molecular null due to a very early stop codon, while sl7 has a missense mutation in the highly conserved Y catalytic domain. Together with in vitro mutagenesis of the residue affected by the sl7 mutation, these results confirm the role of Sl in RTK signaling and provide evidence for two genetically separable PLC-γ-dependent pathways affecting the development of the eye and the wing.
Maximum-Likelihood Estimation of Admixture Proportions From Genetic Data
Authors: Wang Jinliang
Published: April 2021

For an admixed population, an important question is how much genetic contribution comes from each parental population. Several methods have been developed to estimate such admixture proportions, using data on genetic markers sampled from parental and admixed populations. In this study, I propose a likelihood method to estimate jointly the admixture proportions, the genetic drift that occurred to the admixed population and each parental population during the period between the hybridization and sampling events, and the genetic drift in each ancestral population within the interval between their split and hybridization. The results from extensive simulations using various combinations of relevant parameter values show that in general much more accurate and precise estimates of admixture proportions are obtained from the likelihood method than from previous methods. The likelihood method also yields reasonable estimates of genetic drift that occurred to each population, which translate into relative effective sizes (Ne) or absolute average Ne's if the times when the relevant events (such as population split, admixture, and sampling) occurred are known. The proposed likelihood method also has features such as relatively low computational requirement compared with previous ones, flexibility for admixture models, and marker types. In particular, it allows for missing data from a contributing parental population. The method is applied to a human data set and a wolflike canids data set, and the results obtained are discussed in comparison with those from other estimators and from previous studies.
Likelihood-Based Estimation of Microsatellite Mutation Rates
Authors: Whittaker John C , Harbord Roger M , Boxall Nicola , Mackay Ian , Dawson Gary , Sibly Richard M
Published: April 2021

Microsatellites are widely used in genetic analyses, many of which require reliable estimates of microsatellite mutation rates, yet the factors determining mutation rates are uncertain. The most straightforward and conclusive method by which to study mutation is direct observation of allele transmissions in parent-child pairs, and studies of this type suggest a positive, possibly exponential, relationship between mutation rate and allele size, together with a bias toward length increase. Except for microsatellites on the Y chromosome, however, previous analyses have not made full use of available data and may have introduced bias: mutations have been identified only where child genotypes could not be generated by transmission from parents' genotypes, so that the probability that a mutation is detected depends on the distribution of allele lengths and varies with allele length. We introduce a likelihood-based approach that has two key advantages over existing methods. First, we can make formal comparisons between competing models of microsatellite evolution; second, we obtain asymptotically unbiased and efficient parameter estimates. Application to data composed of 118,866 parent-offspring transmissions of AC microsatellites supports the hypothesis that mutation rate increases exponentially with microsatellite length, with a suggestion that contractions become more likely than expansions as length increases. This would lead to a stationary distribution for allele length maintained by mutational balance. There is no evidence that contractions and expansions differ in their step size distributions.
The Effects of Host Age, Host Nuclear Background and Temperature on Phenotypic Effects of the Virulent Wolbachia Strain popcorn in Drosophila melanogaster
Authors: Reynolds K Tracy , Thomson Linda J , Hoffmann Ary A
Published: April 2021

Because of their obligate endosymbiotic nature, Wolbachia strains by necessity are defined by their phenotypic effects upon their host. Nevertheless, studies on the influence of host background and environmental conditions upon the manifestation of Wolbachia effects are relatively uncommon. Here we examine the behavior of the overreplicating Wolbachia strain popcorn in four different Drosophila melanogaster backgrounds at two temperatures. Unlike other strains of Wolbachia in Drosophila, popcorn has a major fitness impact upon its hosts. The rapid proliferation of popcorn causes cells to rupture, resulting in the premature death of adult hosts. Apart from this effect, we found that popcorn delayed development time, and host background influenced both this trait and the rate of mortality associated with infection. Temperature influenced the impact of popcorn upon host mortality, with no reduction in life span occurring in flies reared at 19°. No effect upon fecundity was found. Contrary to earlier reports, popcorn induced high levels of incompatibility when young males were used in tests, and CI levels declined rapidly with male age. The population dynamics of popcorn-type infections will therefore depend on environmental temperature, host background, and the age structure of the population.
Deleterious Mutations and the Genetic Variance of Male Fitness Components in Mimulus guttatus
Authors: Kelly John K
Published: April 2021

Deleterious mutations are relevant to a broad range of questions in genetics and evolutionary biology. I present an application of the “biometric method” for estimating mutational parameters for male fitness characters of the yellow monkeyflower, Mimulus guttatus. The biometric method rests on two critical assumptions. The first is that experimental inbreeding changes genotype frequencies without changing allele frequencies; i.e., there is no genetic purging during the experiment. I satisfy this condition by employing a breeding design in which the parents are randomly extracted, fully homozygous inbred lines. The second is that all genetic variation is attributable to deleterious mutations maintained in mutation-selection balance. I explicitly test this hypothesis using likelihood ratios. Of the three deleterious mutation models tested, the first two are rejected for all characters. The failure of these models is due to an excess of additive genetic variation relative to the expectation under mutation-selection balance. The third model is not rejected for either of two log-transformed male fitness traits. However, this model imposes only “weak conditions” and is not sufficiently detailed to provide estimates for mutational parameters. The implication is that, if biometric methods are going to yield useful parameter estimates, they will need to consider mutational models more complicated than those typically employed in experimental studies.