bluuebunny/crossref_metadata_2025 huggingface dataset:
113 Exploratory laparoscopy in suspected bowel obstruction secondary to a transmesenteric hernia
Authors: Aguilera Beatriz Carrasco , García Miguel Martinez-Cachero , del Val Ruiz Pablo , Prieto Andres Cembellin , Rodicio Miravalles Jose Luis , Granero Trancón Jose Electo
Published: August 2023

Background

Transmesenteric hernias (TH) in adults are an uncommon subtype of internal hernia that can be life-threatening because of the risk of bowel ischemia if not correctly diagnosed.

Case report

A 79-year-old man came to the emergency department with abdominal pain associated with vomiting and constipation for 24 hours. Physical examination showed no alarm signs. However, due to the presence of leukocytosis with neutrophilia and an abdominal X-ray with suspected obstruction, an abdominal CT scan was requested. Given the radiological finding of a defect in the mesentery through which a portion of the mesentery and several loops of bowel were introduced, an exploratory laparoscopy was indicated on suspicion of TH. Intraoperatively, 150 cm from the ileocecal valve, a 30 cm congestive segment of jejunum was observed, which was inserted in a 4 cm long eyelet in the omentum. Reduction of the herniated small bowel loops through the eyelet was performed without difficulty, observing good viability of the loops, and the eyelet was opened with scissors leaving the omentum open at the distal end. The patient was discharged on the 5th postoperative day tolerating oral diet, with transit and the surgical wound without signs of infection.

Conclusion

Although CT is the best diagnostic test for TH its preoperative diagnosis remains difficult. In the case of suspected TH, early exploratory laparoscopy is a correct technique that can preserve the viability of the bowel.
177 Impact of Covid Pandemic on Cholecystectomy Waiting Lists in NHS Highland: Lessons and Opportunities
Authors: Brown Jasmine , Grant Alan , Aboutaleb Esam
Published: August 2023

Aims

The standard waiting time for elective surgery is 18 weeks. However, it continues to face pressure. We aimed to look at:

Methods

Retrospective data of patients listed for a cholecystectomy throughout the health board from April 2019-June 2022 were collected using electronic records. Patients removed from the list were excluded. Data was collected on patient demographics, hospital listed/performed, waiting list length, surgical approach and post-operative outcomes.

Results

278 patients were included. 79% operations were listed centrally with 52% performed there. 72% were female and 28% male. The average age was 53.6 years (22-91).

Of those listed 45% underwent surgery. The average waiting time was 106 days overall (5-1024), 110.5 in 2020, 156 in 2021, 57.5 in 2022, 78% being performed within target. 98.4% were laparoscopic and 1.6% converted. 88% of operations were elective and 12% emergency. 1 patient had malignancy on pathology. 15 patients had complications with 3 bile leaks (2.4%).

22 patients were admitted whilst waiting for a total of 36 days, costing an estimated £14,400. 64% received an emergency operation during admission, all which were performed centrally (p=<0.05)

Length of stay was shorter at C (p=<0.05) and equivalent at B. Complications were lower at C (7.7%) and B (11%) compared to centrally (13%).

Conclusions

Patients are waiting longer for cholecystectomies with increased financial burden. Complications rates have increased, especially bile leaks which needs to be investigated further. Rural hospitals can be safely used to alleviate pressures.
361 A comparison of confidence at the start of a general surgical rotation between first and second rotations of foundation year one doctors in a busy district general hospital
Authors: George Jayan , Savage Daniella , Wafai Ahmad Hisham , Vasas Peter , Yeluri Sashidhar
Published: August 2023

Aims

Methods

FY1 doctors were surveyed in December 2022. Ten questions used Likert scales (1 to 5: not at all confident to very confident) to assess general surgical patient management. One question focused on education methods and one open question. Data was initially inputted using Google Docs and analysed in Microsoft Excel.

Results

10 FY1 doctors (10/10) completed the pre-questionnaire in their first rotation. 6 FY1 doctors (6/9) completed the pre-questionnaire in their second rotation.

All second-rotation respondents had a previous medical rotation.

Confidence levels were higher for FY1 doctors at the start of their second rotation in surgery than those in their first rotation.

Areas, where FY1 doctors in their first rotation had higher confidence levels, were: maintenance fluid therapy, managing biliary disease, managing non-specific abdominal pain and speaking to a patient about their management when their condition is unknown.

Most FY1 doctors in the first rotation felt that case-based discussions would be the preferred method to increase understanding in general surgery whereas most second rotation FY1 doctors preferred method was group teaching would be.

Conclusions

Confidence levels were higher in the doctors on their second rotation than in their first. Further targeted teaching may support increasing confidence before the rotation.
482 A closed loop audit showing learning from the National Audit of Small Bowel Obstruction at a District General Hospital
Authors: Mallon Aoife , Gallagher Charles
Published: August 2023

Aims

The National Audit of Small Bowel Obstruction (NASBO) was a prospective study in 2017 that gave recommendations for small bowel obstruction (SBO) management. Those were; early CT, increased use of water soluble contrast for prognostic and therapeutic purpose, early assessment of nutritional status and involvement of nutritional specialists. Our DGH had not been part of this study so we wanted to compare our practice.

Method

We identified 35 patients from admissions records with SBO over an eight week period and reviewed their online records. We presented the findings of our practice in comparison to NASBO at an Audit and Governance meeting, reiterating the recommendations of NASBO. We closed the loop on this audit one year later, identifying 18 patients on reaudit.

Results

Referrals; ED: (NASBO/ 1st Audit/ Reaudit) 68%/91%/95%, GP: 18%/6%/0%.

Aetiology; herniae 19%/50%/16%, adhesions: 54%/25%/61%.

Management; early surgery: 24%/33%/22%, Conservative: 49%/58%/66%, Delayed surgery: 20%/9%/11%.

Radiology Assessment; CT: 80%/88%/94%, AXR + CT: 65%/75%/88%, Water soluble contrast: 21%/12%/44%, Average days to CT: 2.2/0.18/0.43.

Nutrition; Identified as Malnourished: 32%/6%/5%, No oral intake >5days: 49%/44%/17%, Parenteral Nutrition: 14%/6%/17%.

Outcomes; Death: 8%/9%/10%, Readmission: 13%/0%/22%.

Conclusion

Our results show a lot of similarity to NASBO's despite low admissions. Our department improved upon already high CT rates although we increased our percentage receiving both AXR + CT, ergo higher radiation received. There was a marked increased percentage receiving water soluble contrast, our standout improvement. There was no improvement with our nutritional assessment though an increased percentage received parenteral nutrition.
500 CT imaging requests in Major Trauma Patients
Authors: Marzouqa Natalie
Published: August 2023

Introduction

There is a correlation between adequate CT Trauma orders and accuracy of radiological reporting. In this audit, the aim is to improve accuracy of reporting by following the Royal College of Radiologists (RCR) indications for polytrauma CT imaging in the document ‘Standards of practice and guidance for trauma radiology in severely injured patients, 2nd edition’. Standard 7 in this guidance states that a CT request in the trauma setting should comply with the Ionising Radiation (Medical Exposure) Regulations justification regulations in the same way as any other request for imaging involving ionising radiation.

Method

Clinical information in CT orders of 57 major trauma patients in the East Midlands Major Trauma Centre were reviewed against ‘Standards of practice and guidance for trauma radiology in severely injured patients, 2nd edition’. The request should have two essential pieces of information: mechanism of injury and suspected injuries. In these 57 patient, 96% had appropriate requests. Since the target is 100%, an email was sent out and a teaching session was carried out to improve practice. A second cycle including 80 patients in the same centre was carried out.

Results

Before intervention, 96% of the CT in major trauma patients were compliant with guidelines. After intervention, this improved to 100%.

Conclusion

Compliance with RCR criteria improved after intervention, this surely helped avoid unnecessary radiation exposure and enhanced radiological reporting in major trauma patient scans.
556 Bolam law for medical negligence, external factors and exceptional circumstances: Is this law still fit for the 21st Century? A literature based review
Authors: Magsi Abdul Malik , Qasim Muhammad , Umair Musab Bin , Singh Krishna K , Sajid Muhammad S , Sains Parv
Published: August 2023

Objective

The objective of this article is to evaluate the fitness of Bolam law (1957) for medical negligence under times of great change in healthcare provision, scarcity of resources, rapidly changing technologies, and exceptional circumstances of a pandemic.

Methods

An extensive review of medical and legal literature was undertaken that detailed the Bolam and Bolitho tests of negligence.

Results

For the medical professional, Bolam enhanced certainty by providing medical professionals with confidence that contradictory perspectives would not necessarily be seen in law as evidence of substandard care. From a patient’s perspective, however, Bolam was perceived to have established a climate of deference to the medical profession with an arguable abdication of responsibility to clinicians as the experts. The House of Lords decision (Bolitho v City) in 1997 signalled a shift away from Bolam, possibly having restored it back to its proper limits. Bolitho moved away from the second part of the Bolam test, that of the ‘responsible body of medical men”, ensuring that peer professional opinion which was said to represent evidence of responsible medical practice could be departed from, if that opinion was determined by the court to be “not capable of withstanding logical analysis,” or was otherwise “unreasonable” or “irresponsible.”

Conclusion

Medical negligence is a complex situation that is underpinned by the setting of a standard of care through various mechanisms involving the surgical community, hospital leaders and management, the judiciary, lawyers, and expert witnesses. The current system is adversarial and arguably lacks compassion for all parties.
598 Expediting the journey of venous disease management by adopting (one stop vein clinic)
Authors: Ashoor Yasser
Published: August 2023

Introduction

As a third of the UK's population is estimated to be affected by varicose veins, which cause around 10% of complications, varicose veins represents a significant part of the surgical workload.

To receive their diagnosis and be listed for treatment, patients must attend two outpatient appointments interrupted by ultrasound scans provided by radiographers.

Statistical analysis indicated that there was a significant delay from referral to treatment exceeding eight months as a result of a shortage of radiographers which resulted in a delayed ultrasound.

Aims

Speeding up the management can be achieved by incorporating diagnostic imaging input within the outpatient department by creating a One Stop Clinic where the patient will be examined in the clinic and undergo ultrasound scan by the same vascular surgeon before receiving the management plan in the same setting.

Methods

A project was started on March 2022 by allowing a vascular surgeon to scan patients under supervision of a radiologist till he is confident to perform it independently. Data showed that 111 patients were scanned in 8 months and were provided the decision plan to intervene immediately following the scan. Treatment was received within 6 weeks following the clinic visit.

Conclusion

In addition to benefitting patients by providing immediate management plans and early treatment, one-stop vein clinics will also assist in saving the NHS resources, clinic spaces, and costs. Furthermore, it will reduce the workload of radiographers and assist vascular surgeons in mastering the skills of ultrasound, which are becoming a cornerstone of modern vascular surgery.
Athena: Specialty Certificate Examination case for formulation and systemic therapy
Authors: Tang Gia T , Daunton Adam
Published: August 2023

This Athena details the case of a 53-year-old woman with ongoing hair loss who was taking several medications.
Limb-specific thalamocortical tracts are impaired differently in hemiplegic and diplegic subtypes of cerebral palsy
Authors: Jaatela Julia , Aydogan Dogu Baran , Nurmi Timo , Vallinoja Jaakko , Mäenpää Helena , Piitulainen Harri
Published: August 2023

Thalamocortical pathways are considered crucial in the sensorimotor functioning of children with cerebral palsy (CP). However, previous research has been limited by non-specific tractography seeding and the lack of comparison between different CP subtypes. We compared limb-specific thalamocortical tracts between children with hemiplegic (HP, N = 15) or diplegic (DP, N = 10) CP and typically developed peers (N = 19). The cortical seed-points for the upper and lower extremities were selected (i) manually based on anatomical landmarks or (ii) using functional magnetic resonance imaging (fMRI) activations following proprioceptive-limb stimulation. Correlations were investigated between tract structure (mean diffusivity, MD; fractional anisotropy, FA; apparent fiber density, AFD) and sensorimotor performance (hand skill and postural stability). Compared to controls, our results revealed increased MD in both upper and lower limb thalamocortical tracts in the non-dominant hemisphere in HP and bilaterally in DP subgroup. MD was strongly lateralized in participants with hemiplegia, while AFD seemed lateralized only in controls. fMRI-based tractography results were comparable. The correlation analysis indicated an association between the white matter structure and sensorimotor performance. These findings suggest distinct impairment of functionally relevant thalamocortical pathways in HP and DP subtypes. Thus, the organization of thalamocortical white matter tracts may offer valuable guidance for targeted, life-long rehabilitation in children with CP.
Inhibition of galectin-3 post-infarction impedes progressive fibrosis by regulating inflammatory profibrotic cascades
Authors: Wang Xiaoyin , Gaur Meenakshi , Mounzih Khalid , Rodriguez Hilda J , Qiu Huiliang , Chen Ming , Yan Liqiu , Cooper Brian A , Narayan Shilpa , Derakhshandeh Ronak , Rao Poonam , Han Daniel D , Nabavizadeh Pooneh , Springer Matthew L , John Constance M
Published: August 2023

Aims

Acute myocardial infarction (MI) causes inflammation, collagen deposition, and reparative fibrosis in response to myocyte death and, subsequently, a pathological myocardial remodelling process characterized by excessive interstitial fibrosis, driving heart failure (HF). Nonetheless, how or when to limit excessive fibrosis for therapeutic purposes remains uncertain. Galectin-3, a major mediator of organ fibrosis, promotes cardiac fibrosis and remodelling. We performed a preclinical assessment of a protein inhibitor of galectin-3 (its C-terminal domain, Gal-3C) to limit excessive fibrosis resulting from MI and prevent ventricular enlargement and HF.

Methods and results

Gal-3C was produced by enzymatic cleavage of full-length galectin-3 or by direct expression of the truncated form in Escherichia coli. Gal-3C was intravenously administered for 7 days in acute MI models of young and aged rats, starting either pre-MI or 4 days post-MI. Echocardiography, haemodynamics, histology, and molecular and cellular analyses were performed to assess post-MI cardiac functionality and pathological fibrotic progression. Gal-3C profoundly benefitted left ventricular ejection fraction, end-systolic and end-diastolic volumes, haemodynamic parameters, infarct scar size, and interstitial fibrosis, with better therapeutic efficacy than losartan and spironolactone monotherapies over the 56-day study. Gal-3C therapy in post-MI aged rats substantially improved pump function and attenuated ventricular dilation, preventing progressive HF. Gal-3C in vitro treatment of M2-polarized macrophage-like cells reduced their M2-phenotypic expression of arginase-1 and interleukin-10. Gal-3C inhibited M2 polarization of cardiac macrophages during reparative response post-MI. Gal-3C impeded progressive fibrosis post-MI by down-regulating galectin-3-mediated profibrotic signalling cascades including a reduction in endogenous arginase-1 and inducible nitric oxide synthase (iNOS).

Conclusion

Gal-3C treatment improved long-term cardiac function post-MI by reduction in the wound-healing response, and inhibition of inflammatory fibrogenic signalling to avert an augmentation of fibrosis in the periinfarct region. Thus, Gal-3C treatment prevented the infarcted heart from extensive fibrosis that accelerates the development of HF, providing a potential targeted therapy.
C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway
Authors: Liu Aiting , Chen Zhenwei , Li Xiaoxue , Xie Chen , Chen Yanlian , Su Xiaoyan , Chen Ying , Zhang Mengbi , Chen Jie , Yang Tiecheng , Shen Jiangang , Huang Hui
Published: August 2023

Aims

Vascular calcification (VC) predicts the morbidity and mortality in cardiovascular diseases. Vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation is the crucial pathological basis for VC. To date, the molecular pathogenesis is still largely unclear. Notably, C5a-C5aR1 contributes to the development of cardiovascular diseases, and its closely related to physiological bone mineralization which is similar to VSMCs osteogenic transdifferentiation. However, the role and underlying mechanisms of C5a-C5aR1 in VC remain unexplored.

Methods and results

A cross-sectional clinical study was utilized to examine the association between C5a and VC. Chronic kidney diseases mice and calcifying VSMCs models were established to investigate the effect of C5a-C5aR1 in VC, evaluated by changes in calcium deposition and osteogenic markers. The cross-sectional study identified that high level of C5a was associated with increased risk of VC. C5a dose-responsively accelerated VSMCs osteogenic transdifferentiation accompanying with increased the expression of C5aR1. Meanwhile, the antagonists of C5aR1, PMX 53, reduced calcium deposition, and osteogenic transdifferentiation both in vivo and in vitro. Mechanistically, C5a-C5aR1 induced endoplasmic reticulum (ER) stress and then activated PERK-eIF2α-ATF4 pathway to accelerated VSMCs osteogenic transdifferentiation. In addition, cAMP-response element-binding protein 3-like 1 (CREB3L1) was a key downstream mediator of PERK-eIF2α-ATF4 pathway which accelerated VSMCs osteogenic transdifferentiation by promoting the expression of COL1α1.

Conclusions

High level of C5a was associated with increased risk of VC, and it accelerated VC by activating the receptor C5aR1. PERK-eIF2α-ATF4-CREB3L1 pathway of ER stress was activated by C5a-C5aR1, hence promoting VSMCs osteogenic transdifferentiation. Targeting C5 or C5aR1 may be an appealing therapeutic target for VC.
Outcomes Following Acute Severe Colitis at Initial Presentation: A Multi-centre, Prospective, Paediatric Cohort Study
Authors: Dhaliwal Jasbir , Tertigas Dominique , Carman Nicholas , Lawrence Sally , Debruyn Jennifer C , Wine Eytan , Church Peter C , Huynh Hien Q , Rashid Mohsin , El-Matary Wael , Deslandres Colette , Critch Jeffrey , Ricciuto Amanda , Carroll Matthew W , Benchimol Eric I , Muise Aleixo , Jacobson Kevan , Otley Anthony R , Vallance Bruce , Mack David R , Walters Thomas D , Surette Michael G , Griffiths Anne M
Published: August 2023

Aim

To assess contemporary outcomes in children with acute severe ulcerative colitis [ASUC] at initial presentation.

Methods

Between April 2014 and January 2019, children aged <17 years, with new onset ASUC (Paediatric Ulcerative Colitis Activity Index [PUCAI ≥65) were prospectively followed in a Canadian inception cohort study. 16S rRNA amplicon sequencing captured microbial composition of baseline faecal samples. Primary endpoint was corticosteroid-free clinical remission with intact colon at 1 year [PUCAI <10, no steroids ≥4 weeks].

Results

Of 379 children with new onset UC/IBD-unclassified, 105 [28%] presented with ASUC (42% male; median [interquartile range; [IQR]) age 14 [11-16] years; extensive colitis in all). Compared with mild UC, gut microbiome of ASUC patients had lower α-diversity, decreased beneficial anaerobes, and increased aerobes; 54 [51%] children were steroid-refractory and given infliximab [87% intensified regimen]. Corticosteroid-free remission at 1 year was achieved by 62 [61%] ASUC cohort (by 34 [63%] steroid-refractory patients, all on biologics; by 28 [55%] steroid responders,13 [25%] on 5- aminosalicylic acid [5-ASA], 5 [10%] on thiopurines, 10 [20%] on biologics). By 1 year, 78 [74%] escalated to infliximab including 24 [47%] steroid-responders failed by 5-ASA and/or thiopurines. In multivariable analysis, clinical predictors for commencing infliximab included hypoalbuminaemia, greater PUCAI, higher age, and male sex. Over 18 months, repeat corticosteroid course[s] and repeat hospitalisation were less likely among steroid-refractory versus -responsive but -dependent patients (adjusted odds ratio [aOR] 0.71 [95% CI 0.57-0.89] and 0.54 [95% CI 0.45-0.66], respectively).

Conclusion

The majority of children presenting with ASUC escalate therapy to biologics. Predictors of need for advanced therapy may guide selection of optimal maintenance therapy.
A novel approach to hypophysitis: outcomes using non-glucocorticoid immunosuppressive therapy
Authors: Vakharia Janaki D , Muhammed Maged , Remba-Shapiro Ilan , Marsiglia Marcela , Hadaway Natalia , Chwalisz Bart K , Nachtigall Lisa B
Published: August 2023

Objective

To determine pituitary function before and after nonglucocorticoid immunosuppressive therapy (NGIT) in subjects with hypophysitis and evaluate their clinical and radiologic outcomes.

Design

Retrospective, longitudinal study.

Methods

We reviewed a large database, selected subjects with hypophysitis treated with NGIT, and collected information on the duration of therapy, and clinical, hormonal, and radiologic outcomes.

Results

Twelve subjects met the inclusion criteria. Five subjects had primary hypophysitis (PH), while seven had secondary hypophysitis (SH) due to an underlying systemic inflammatory disease. Mean age ± SD was 48.0 ± 15.7 years and 40.9 ± 13.0 years, for PH and SH, respectively. The majority were female (PH 60% and SH 86%). BMI ± SD at presentation was 25.2 ± 2.5 kg/m2 and 26.8 ± 6.7 kg/m2 for PH and SH, respectively. The most common symptom at presentation was fatigue (75%). All PH subjects (100%) and 2 (28.6%) SH subjects had polyuria/polydipsia. There was a significant decrease in mean pituitary stalk thickness after NGIT (P = .0051) (mean duration 16.5 ± 4.8 months). New hormone loss or recovery occurred rarely. Mycophenolate mofetil was the most used NGIT: adverse effects prompted discontinuation in 2 out of 7 subjects.

Conclusions

Subjects with hypophysitis receiving NGIT had stable or improved brain/pituitary magnetic resonance imaging findings with a significant decrease in pituitary stalk thickness. NGITs did not improve anterior pituitary function. Our findings suggest that NGIT may be considered as an alternative therapy for patients with hypophysitis who require immunosuppression.
Time on the crossing: emigrant voyages across the Atlantic, 1853–1913
Authors: Hatton Timothy J
Published: August 2023

I provide a new series of the average duration of emigrant voyages from Liverpool to New York from 1853 to 1913. Time on the crossing fell by 80 percent, from about 40 days to just eight, most of which occurred in the first 2 decades and was associated with the transition from sail to steam. The standard deviation of voyage durations also dramatically decreased. Although average transatlantic fares did not fall, if foregone earnings during the voyage are included, the total cost declined until the early 1900s, and especially so when measured in terms of the number of weeks’ work.
Lending a hand: help banks in the Netherlands, 1848–1898
Authors: de Vicq Amaury , van Bochove Christiaan
Published: August 2023

Households and small businesses are often confronted with funding gaps due to small-scale lending problems. Whereas existing research focused primarily on how rural areas addressed such problems, this paper determines what contributed to the success of urban help banks in the Netherlands (1848–1898). It considers how help banks’ lending mechanism, corporate governance mechanism, and historical circumstances lowered operating costs. The latter was crucial and depended on elites with philanthropic and practical considerations, who housed, staffed, and funded help banks at modest costs. This mix provides guidance to small-scale lenders, including microcredit institutions, to address funding gaps and tailor their services.
Educational achievement of children with selected major congenital anomalies and associated factors: a Finnish registry-based study
Authors: Roustaei Zahra , Heino Anna , Kiuru-Kuhlefelt Sonja , Morris Joan K , Glinianaia Svetlana V , Garne Ester , Loane Maria , Rankin Judith , Gissler Mika
Published: August 2023

Background

Children with major congenital anomalies may be at risk of poor educational outcomes. We aimed to evaluate the educational achievement of children born with major congenital anomalies compared with children without major congenital anomalies in relation to sociodemographic factors.

Methods

We performed a registry-based study including 401 544 children in Finland, graduates of the compulsory school who applied to secondary education. We used health data from the Finnish Register of Congenital Malformations for children born from 1995 to 2002 linked with education data from the Finnish Ministry of Education and Culture. We used generalized linear regression to compare the mean grade differences of children with specific major congenital anomalies and ‘All anomalies’ subgroup (major congenital anomalies, chromosomal syndromes, and multiple anomalies) with reference children.

Results

Children with major congenital anomalies were less likely to apply for further education than reference children (88.0% vs. 96.8%; odds ratio = 4.13; 95% confidence interval, 3.92–4.36). For most non-chromosomal congenital anomalies, children born with congenital anomalies had similar educational achievement to the reference children. For the ‘All anomalies’ subgroup, children with congenital anomalies had lower educational achievement than reference children. Among children with congenital anomalies, male sex, lower maternal educational levels and younger maternal age were associated with lower educational achievement.

Conclusions

For children applying to further education, most non-chromosomal congenital anomalies were not associated with lower educational achievement. Nevertheless, efforts are needed to improve educational achievement in children with major congenital anomalies associated with maternal sociodemographic background.
Genomic mechanisms and consequences of diverse postzygotic barriers between monkeyflower species
Authors: Sotola V Alex , Berg Colette S , Samuli Matthew , Chen Hongfei , Mantel Samuel J , Beardsley Paul A , Yuan Yao-Wu , Sweigart Andrea L , Fishman Lila
Published: August 2023

The evolution of genomic incompatibilities causing postzygotic barriers to hybridization is a key step in species divergence. Incompatibilities take 2 general forms—structural divergence between chromosomes leading to severe hybrid sterility in F1 hybrids and epistatic interactions between genes causing reduced fitness of hybrid gametes or zygotes (Dobzhansky–Muller incompatibilities). Despite substantial recent progress in understanding the molecular mechanisms and evolutionary origins of both types of incompatibility, how each behaves across multiple generations of hybridization remains relatively unexplored. Here, we use genetic mapping in F2 and recombinant inbred line (RIL) hybrid populations between the phenotypically divergent but naturally hybridizing monkeyflowers Mimulus cardinalis and M. parishii to characterize the genetic basis of hybrid incompatibility and examine its changing effects over multiple generations of experimental hybridization. In F2s, we found severe hybrid pollen inviability (<50% reduction vs parental genotypes) and pseudolinkage caused by a reciprocal translocation between Chromosomes 6 and 7 in the parental species. RILs retained excess heterozygosity around the translocation breakpoints, which caused substantial pollen inviability when interstitial crossovers had not created compatible heterokaryotypic configurations. Strong transmission ratio distortion and interchromosomal linkage disequilibrium in both F2s and RILs identified a novel 2-locus genic incompatibility causing sex-independent gametophytic (haploid) lethality. The latter interaction eliminated 3 of the expected 9 F2 genotypic classes via F1 gamete loss without detectable effects on the pollen number or viability of F2 double heterozygotes. Along with the mapping of numerous milder incompatibilities, these key findings illuminate the complex genetics of plant hybrid breakdown and are an important step toward understanding the genomic consequences of natural hybridization in this model system.
Safety, Effectiveness, and Treatment Persistence of Subcutaneous Vedolizumab in IBD: A Multicenter Study From the United Kingdom
Authors: Lim Samuel Hsiang , Gros Beatriz , Sharma Esha , Lehmann Anouk , Lindsay James O , Caulfield Louise , Gaya Daniel R , Taylor Jo , Limdi Jimmy , Kwok Jon , Shuttleworth Elinor , Dhar Anjan , Burdge Gemma , Selinger Christian , Cococcia Sara , Murray Charles , Balendran Karthiha , Raine Tim , George Becky , Walker Gareth , Aldridge Robin , Irving Peter , Lees Charlie W , Samaan Mark
Published: August 2023

Background and Aims

Despite intravenous (IV) vedolizumab being established for treatment of inflammatory bowel disease (IBD), the novel subcutaneous (SC) route of administration may provide numerous incentives to switch. However, large-scale real-world data regarding the long-term safety and effectiveness of this strategy are lacking.

Methods

IBD patients on IV vedolizumab across 11 UK sites agreed to transition to SC injections or otherwise continued IV treatment. Data regarding clinical disease activity (Simple Clinical Colitis Activity Index, partial Mayo score, and modified Harvey-Bradshaw Index), biochemical markers (C-reactive protein and calprotectin), quality of life (IBD control), adverse events, treatment persistence, and disease-related outcomes (namely corticosteroid use, IBD-related hospitalization, and IBD-related surgery) were retrospectively collected from prospectively maintained clinical records at baseline and weeks 8, 24, and 52.

Results

Data from 563 patients (187 [33.2%] Crohn’s disease, 376 [66.8%] ulcerative colitis; 410 [72.8%] SC, 153 [27.2%] IV) demonstrated no differences in disease activity, remission rates, and quality of life between the SC and IV groups at all time points. Drug persistence at week 52 was similar (81.1% vs 81.2%; P = .98), as were rates of treatment alteration due to either active disease (12.2% vs 8.9%; P = .38) or adverse events (3.3% vs 6.3%; P = .41). At week 52, there were equivalent rates of adverse events (9.8% vs 7.8%; P = .572) and disease-related outcomes. IBD control scores were equivalent in both IV-IV and IV-SC groups.

Conclusions

Switching to SC vedolizumab appears as effective, safe, and well tolerated as continued IV treatment and maintains comparable disease control and quality of life as IV treatment at 52 weeks.
Floating offshore wind farms in Mediterranean marine protected areas: a cautionary tale
Authors: Lloret Josep , Wawrzynkowski Paul , Dominguez-Carrió Carlos , Sardá Rafael , Molins Climent , Gili Josep Maria , Sabatés Ana , Vila-Subirós Josep , Garcia Laura , Solé Jordi , Berdalet Elisa , Turiel Antonio , Olivares Alberto
Published: August 2023

As offshore wind energy expands in Europe, maritime planners increasingly need to consider the potential effects of these activities on the different types of marine protected areas (MPAs), including Natura 2000 sites. The aim of this article is to critically review the initial development of offshore wind energy inside and/or in the vicinity of Mediterranean Natura 2000 sites and other types of MPAs. The western Mediterranean Sea is taken as an example as this is where most of the offshore wind developments have been proposed. In order to open up discussion of offshore wind energy policy and guide ecological research that supports holistic decisions regarding offshore wind farm (OWF) installation in the region, we (i) outline the context of Natura 2000 and other MPA policy in the Mediterranean for OWF development, (ii) summarize the potential impacts of OWF on EU-protected habitats and species, (iii) assess the interactions of OWFs, the Natura 2000 sites, and other MPAs, and (iv) propose recommendations to approach OWF development in the Mediterranean in order to safeguard the Natura 2000 sites and other MPAs. After documenting the potential overlaps between OWFs and MPAs in the western Mediterranean, we recommend OWFs be placed outside Natura 2000 and other MPA sites, including their buffer zones. We also advocate for rigorous and independent Appropriate Assessments to be carried out for OWF proposals that could affect protected areas.
Association of Prolactin, Oxytocin, and Homocysteine With the Clinical and Cognitive Features of a First Episode of Psychosis Over a 1-Year Follow-Up
Authors: Hidalgo-Figueroa Maria , Salazar Alejandro , Romero-López-Alberca Cristina , MacDowell Karina S , García-Bueno Borja , Bioque Miquel , Bernardo Miquel , Parellada Mara , González-Pinto Ana , García-Portilla M Paz , Lobo Antonio , Rodriguez-Jimenez Roberto , Berrocoso Esther , Leza Juan C ,   FLAMM-PEPs study,   CIBERSAM
Published: August 2023

Background

The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics.

Methods

We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features.

Results

At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients.

Conclusion

This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind.
Establishing a clinical informatics umbilical cord: lessons learned in launching infrastructure to support dyadic mother/infant primary care
Authors: Bose-Brill Seuli , D’Amico Rachel , Bartley Adam , Ashmead Robert , Flores-Beamon Paola , Jallaq Shadia , Li Kevin , Mao Shengyi , Gillespie Shannon , Fareed Naleef , Venkatesh Kartik K , Crossnohere Norah L , Davis Jody , Bunger Alicia C , Lorenz Allison
Published: August 2023

The Multimodal Maternal Infant Perinatal Outpatient Delivery System (MOMI PODS) was developed to facilitate the pregnancy to postpartum primary care transition, particularly for individuals at risk for severe maternal morbidity, via a unique multidisciplinary model of mother/infant dyadic primary care. Specialized clinical informatics platforms are critical to ensuring the feasibility and scalability of MOMI PODS and a smooth perinatal transition into longitudinal postpartum primary care. In this manuscript, we describe the MOMI PODS transition and management clinical informatics platforms developed to facilitate MOMI PODS referrals, scheduling, evidence-based multidisciplinary care, and program evaluation. We discuss opportunities and lessons learned associated with our applied methods, as advances in clinical informatics have considerable potential to enhance the quality and evaluation of innovative maternal health programs like MOMI PODS.
Short-term changes in dietary fat levels and starch sources affect weight management, glucose and lipid metabolism, and gut microbiota in adult cats
Authors: Mo Ruixia , Zhang Mingrui , Wang Haotian , Liu Tianyi , Zhang Gang , Wu Yi
Published: August 2023

A 2 × 2 factorial randomized design was utilized to investigate the effects of fat level (8% or 16% fat on a fed basis) and starch source (pea starch or corn starch) on body weight, glycolipid metabolism, hematology, and fecal microbiota in cats. The study lasted for 28 d and included a low fat and pea starch diet (LFPS), a high fat and pea starch diet, a low fat and corn starch diet, and a high fat and corn starch diet. In this study, hematological analysis showed that all cats were healthy. The apparent total tract digestibility of gross energy, crude protein, and crude fat was above 85% in the four diets. After 28 d, cats fed the high fat diets (HF) gained an average of 50 g more than those fed the low fat diets (LF). The hematological results showed that the HF diets increased the body inflammation in cats, while the LFPS group improved the glucolipid metabolism. The levels of glucose and insulin were lower in cats fed the LF diets than those in cats fed the HF diets (P < 0.05). Meanwhile, compared with the LF, the concentrations of total cholesterol, triglyceride, and high-density lipoprotein cholesterol in serum were greater in the cats fed the HF diets (P < 0.05). Additionally, both fat level and starch source influenced the fecal microbiota, with the relative abundance of beneficial bacteria, such as Blautia being significantly greater in the LFPS group than in the other three groups (P < 0.05). Reducing energy density and using pea starch in foods are both valuable design additions to aid in the management of weight control and improve gut health in cats. This study highlights the importance of fat level and starch in weight management in cats.
Adjuvant and neoadjuvant chemotherapy for biliary tract cancer: a review of randomized controlled trials
Authors: Nakachi Kohei , Gotohda Naoto , Hatano Etsuro , Nara Satoshi , Takahashi Shinichiro , Kawamoto Yasuyuki , Ueno Makoto
Published: August 2023

The first randomized controlled trial of adjuvant chemotherapy for biliary tract cancer was reported in 2002. Since then, studies have continued, with efficacy reported for capecitabine in 2018 and S-1 in 2023. Oral fluoropyrimidines have become established as the standard of care. This article reviews the evidence from the randomized controlled trials reported to date and those that are ongoing or from which results have not yet been reported.
Women in U.S. Law Schools, 1948–2021
Authors: Katz Elizabeth D , Rozema Kyle , Sanga Sarath
Published: August 2023

We study the progress of women’s representation and achievement in law schools. To do this, we assemble a new dataset on the number of women and men students, faculty, and deans at all ABA-approved U.S. law schools from 1948 to the present. These data enable us to study many unexplored features of women’s progress in law schools for the first time, including the process by which women initially gained access to each law school, the variance in women’s experiences across law schools, the relationship between women’s representation and student achievement, and the extent to which women disproportionally occupy interim and non-tenure track positions. We contextualize our findings by situating them within the vast qualitative literature on women’s experiences in law schools and the legal profession.
High-resolution emission spectroscopy retrievals of MASCARA-1b with CRIRES+: strong detections of CO, H2O, and Fe emission lines and a C/O consistent with solar
Authors: Ramkumar Swaetha , Gibson Neale P , Nugroho Stevanus K , Maguire Cathal , Fortune Mark
Published: August 2023

The characterization of exoplanet atmospheres has proven to be successful using high-resolution spectroscopy. Phase curve observations of hot/ultra-hot Jupiters can reveal their compositions and thermal structures, thereby allowing the detection of molecules and atoms in the planetary atmosphere using the cross-correlation technique. We present pre-eclipse observations of the ultra-hot Jupiter, MASCARA-1b, observed with the recently upgraded CRIRES+ high-resolution infrared spectrograph at the VLT. We report a detection of Fe (≈ 8.3σ) in the K-band and confirm previous detections of CO (>15σ) and H2O (>10σ) in the day-side atmosphere of MASCARA-1b. Using a Bayesian inference framework, we retrieve the abundances of the detected species and constrain planetary orbital velocities, T–P profiles, and the carbon-to-oxygen ratio (C/O). A free retrieval results in an elevated CO abundance ($\log _{10}(\chi _{\rm {{}^{12}CO}}) = -2.85^{+0.57}_{-0.69}$), leading to a supersolar C/O ratio. More realistically, allowing for vertically-varying chemistry in the atmosphere by incorporating a chemical-equilibrium model results in a C/O of $0.68^{+0.12}_{-0.22}$ and a metallicity of $[\rm M/H] = 0.62^{+0.28}_{-0.55}$, both consistent with solar values. Finally, we also report a slight offset of the Fe feature in both Kp and vsys that could be a signature of atmospheric dynamics. Due to the 3D structure of exoplanet atmospheres and the exclusion of time/phase dependence in our 1D forward models, further follow-up observations and analysis are required to confirm or refute this result.
Genetic Architecture of Flowering Time Differs Between Populations With Contrasting Demographic and Selective Histories
Authors: Neto Célia , Hancock Angela
Published: August 2023

Understanding the evolutionary factors that impact the genetic architecture of traits is a central goal of evolutionary genetics. Here, we investigate how quantitative trait variation accumulated over time in populations that colonized a novel environment. We compare the genetic architecture of flowering time in Arabidopsis populations from the drought-prone Cape Verde Islands and their closest outgroup population from North Africa. We find that trait polygenicity is severely reduced in the island populations compared to the continental North African population. Further, trait architectures and reconstructed allelic histories best fit a model of strong directional selection in the islands in accord with a Fisher–Orr adaptive walk. Consistent with this, we find that large-effect variants that disrupt major flowering time genes (FRI and FLC) arose first, followed by smaller effect variants, including ATX2 L125F, which is associated with a 4-day reduction in flowering time. The most recently arising flowering time-associated loci are not known to be directly involved in flowering time, consistent with an omnigenic signature developing as the population approaches its trait optimum. Surprisingly, we find no effect in the natural population of EDI-Cvi-0 (CRY2 V367M), an allele for which an effect was previously validated by introgression into a Eurasian line. Instead, our results suggest the previously observed effect of the EDI-Cvi-0 allele on flowering time likely depends on genetic background, due to an epistatic interaction. Altogether, our results provide an empirical example of the effects demographic history and selection has on trait architecture.
HELZ2: a new, interferon-regulated, human 3′-5′ exoribonuclease of the RNB family is expressed from a non-canonical initiation codon
Authors: Huntzinger Eric , Sinteff Jordan , Morlet Bastien , Séraphin Bertrand
Published: August 2023

Proteins containing a RNB domain, originally identified in Escherichia coli RNase II, are widely present throughout the tree of life. Many RNB proteins have 3′-5′ exoribonucleolytic activity but some have lost catalytic activity during evolution. Database searches identified a new RNB domain-containing protein in human: HELZ2. Analysis of genomic and expression data combined with evolutionary information suggested that the human HELZ2 protein is produced from an unforeseen non-canonical initiation codon in Hominidae. This unusual property was confirmed experimentally, extending the human protein by 247 residues. Human HELZ2 was further shown to be an active ribonuclease despite the substitution of a key residue in its catalytic center. HELZ2 RNase activity is lost in cells from some cancer patients as a result of somatic mutations. HELZ2 harbors also two RNA helicase domains and several zinc fingers and its expression is induced by interferon treatment. We demonstrate that HELZ2 is able to degrade structured RNAs through the coordinated ATP-dependent displacement of duplex RNA mediated by its RNA helicase domains and its 3′-5′ ribonucleolytic action. The expression characteristics and biochemical properties of HELZ2 support a role for this factor in response to viruses and/or mobile elements.
Structural and functional characterization of MrpR, the master repressor of the Bacillus subtilis prophage SPβ
Authors: Kohm Katharina , Jalomo-Khayrova Ekaterina , Krüger Aileen , Basu Syamantak , Steinchen Wieland , Bange Gert , Frunzke Julia , Hertel Robert , Commichau Fabian M , Czech Laura
Published: August 2023

Prophages control their lifestyle to either be maintained within the host genome or enter the lytic cycle. Bacillus subtilis contains the SPβ prophage whose lysogenic state depends on the MrpR (YopR) protein, a key component of the lysis-lysogeny decision system. Using a historic B. subtilis strain harboring the heat-sensitive SPβ c2 mutant, we demonstrate that the lytic cycle of SPβ c2 can be induced by heat due to a single nucleotide exchange in the mrpR gene, rendering the encoded MrpRG136E protein temperature-sensitive. Structural characterization revealed that MrpR is a DNA-binding protein resembling the overall fold of tyrosine recombinases. MrpR has lost its recombinase function and the G136E exchange impairs its higher-order structure and DNA binding activity. Genome-wide profiling of MrpR binding revealed its association with the previously identified SPbeta repeated element (SPBRE) in the SPβ genome. MrpR functions as a master repressor of SPβ that binds to this conserved element to maintain lysogeny. The heat-inducible excision of the SPβ c2 mutant remains reliant on the serine recombinase SprA. A suppressor mutant analysis identified a previously unknown component of the lysis-lysogeny management system that is crucial for the induction of the lytic cycle of SPβ.