bluuebunny/crossref_metadata_2025 huggingface dataset:
BN SO33 - The complex benign multi-disciplinary team meeting - a paradigm shift in decision making for benign oesophagogastric surgery
Authors: Arkle Thomas , Sivarajan Sri , Yordzheva Petya , Penney Nicholas , Sreedharan Loveena , Kumar Bhaskar
Published: November 2024

Background

Decision making in benign OG pathology can be particularly challenging given the overlap with functional disorders, such as reflux hypersensitivity. A specialist benign oesophagogastric (OG) multidisciplinary team (MDT) may improve our ability to triage potential surgical candidates from those with functional conditions. Unlike in OG cancer, there is a paucity of evidence to support an MDT based approach in benign OG surgery.

This study aims to report our experience of introducing a specialist benign OG MDT in an OG tertiary centre in the UK, examining the effect on decision making and an assessment of its acceptability and utility to clinicians.

Method

A review of consecutive cases discussed in the specialist benign OG MDT since inception in 2022 was undertaken. We reviewed indications, treatment plans and outcomes, any alteration in treatment pathway and final decisions.

The primary outcome was the proportion of patients with a change in management as a result of MDT discussion. Where applicable, results were reported using descriptive statistics. A seven-item electronic questionnaire was also circulated to MDT members (OG surgeons, specialist gastroenterologists, GI radiographers, GI physiologists, and doctors in training), to assess the acceptability and perceived utility of the meetings.

Results

74 patient cases were discussed (median age 57.5 (25-79) years). 71/74 (96.0%) of referrals were made by OG surgeons, most commonly to discuss anti-reflux procedures (53/74 (71.6%)). 34/74 (45.9%) patients had undergone previous surgery, most commonly laparoscopic fundoplication. MDT discussion led to a change in management in 43/74 (58.1%) case with recommendations of further investigation (23.0%), further OG clinic review (18.9%) and 21.6% listed for surgery. 12/74 (16.2%) were referred to other specialist services, including clinical psychology. Survey confirmed that all MDT members found their understanding of oesophageal physiology and subsequent decision-making ability in clinic was greatly enhanced.

Conclusion

Our results show that the complex benign MDT is an effective tool, demonstrating changes to management in over half of cases discussed, including recommending surgery less frequently following specialist review of physiology investigations. Such tests effectively identify functional disorders, such as rumination, highlighting a need for clear onward referral pathways involving specialist psychologists. The meetings have also proven to be valuable learning tools for all attendees of all grades.

We strongly believe that adopting an MDT approach to benign OG conditions will enhance collaborative decision making, improve patient outcomes and therefore should be nationally mandated and recommended through AUGIS guidelines.
HPB SO29 - Outcomes of Percutaneous Image-Guided and Laparoscopic Cholecystostomies in High-Risk Patients With Acute Calculus Cholecystitis: A Five-Year District General Hospital Experience
Authors: Jamal Zohaib , Aly Mahmoud , Khawaja Zeeshan , Zafar Nowera , Kieu Phuong , Kanakalingam Divya , Khalil Ahmed
Published: November 2024

Background

Acute cholecystitis (AC), inflammation of the gall bladder, is one of the most common emergency surgical presentations. In the UK, approximately 15% of the population is estimated to have gallstones, and approximately 20% of them can develop AC. Laparoscopic cholecystectomy (LC) is considered the definitive management of AC. However, cholecystectomy carries a very high risk of morbidity and mortality in high-risk frail patients with multiple comorbidities who are deemed unfit for surgery. Percutaneous cholecystostomy (PC), both image-guided and laparoscopic, is generally acknowledged as an interim treatment measure before definitive management, which is the LC.

Method

This retrospective study from the Royal Albert Edward Infirmary in Wigan, UK, analyzed medical records of patients who underwent percutaneous cholecystostomy (PC) between January 2017 and December 2022. Excluded were patients with prior hepato-pancreato-biliary malignancy, those who had open cholecystostomy, or those with abdominal ascites. Data collected included age, gender, American Society of Anaesthesiologists (ASA) grades, procedure success rates (temporary or definitive), hospital stay duration, 30-day and 1-year mortality rates, timing of the procedure, and long-term complications, particularly those related to cholecystostomy tube dislodgment or blockage.

Results

In this study, 27 patients who underwent percutaneous cholecystostomy (PC) were divided into two groups: Group A (10 patients) had laparoscopic cholecystostomies, and Group B (17 patients) had ultrasound-guided cholecystostomies. The mean ages were 66.7 for Group A and 75.1 for Group B. Most patients were in ASA groups III (14) and IV (10). About 74% had procedures during the day, 26% at night. The mean hospital stay was 13.5 days. Around 55% had elective laparoscopic cholecystectomy (LC) as definitive management. Two patients died within 30 days, and eight within a year. About 40% experienced tube dislodgment or blockage complications.

Conclusion

This study concludes that PC, using both laparoscopic and US-guided techniques, can serve as an interim as well as a definitive measure, particularly in patients who are at high risk for anesthesia and the procedure itself and have multiple comorbidities.
HPB SO46 - Risk Stratification for Acute Pancreatitis: A Retrospective Comparative Analysis between Glasgow-Imrie and BISAP Scoring Systems within a District General Hospital
Authors: Soon Chee Yen , Peters Paul , Yahia Zoubaida , Stringer Samuel , Alam Imran
Published: November 2024

Background

Risk stratification for acute pancreatitis (AP) is an important tool in clinical decision making. The BISAP score has been validated to be a comparable risk prognostication tool to current models[1, 2]. Current trust practice is the Glasgow-Imrie score, which involves more invasive and non-routine investigations, resulting in an increased cost and labour burden. Additionally, a previous local audit demonstrated poor compliance with only 55% of admissions having a documented score, limiting utility and prognostication. By demonstrating non-inferiority, we aim to implement BISAP as the standard of practice with earlier severity assessment, improved patient experience and minimising unnecessary investigations.

Method

A retrospective analysis of 153 admissions with acute pancreatitis admitted to a single-site district general hospital over a 12-month period was performed, reviewing electronic patient records for documentation, observations and investigations. Both Glasgow-Imrie and BISAP scores were calculated within 48 and 24 hours of admission retrospectively and respectively. Descriptive statistics was used to summarise data and compare trends between both scores and the severity of acute pancreatitis, ICU admissions and mortality. Logistic regression was utilised to model the relationship between both systems and binary outcomes with area under the curve (AUC) and non-inferiority tests derived to determine efficacy.

Results

The cohort had a mean age of 57 ± 18.53 (52:48 male:female) with an average LOS of 7.25 ± 10.12 days. 6.54% had severe AP, 3.92% required ICU admisison and 3.26% mortality rate. The AUC value for both models was 0.868 in predicting severity (p<0.001) with Glasgow-Imrie performing better in predicting ICU admission (AUC 0.954 > 0.855, p<0.01) and BISAP outperforming Glasgow-Imrie in predicting mortality (AUC 0.903 > 0.867, p<0.01). Bootstrapping resampling demonstrated no significant difference between models in predicting severity (δAUC 0.0007, 95%CI -0.01181, 0.1167), ICU admission (δAUC 0.1010, 95%CI -0.0113, 0.2140) and mortality (δAUC -0.0366, 95%CI -0.0788, 0.0045).

Conclusion

Both the Glasgow-Imrie and BISAP scoring systems are accurate in predicting the severity of pancreatitis, ICU admission and mortality. The BISAP score is similar in prognostic accuracy to the Glasgow-Imrie score and is advantageous in being simpler to obtain in clinical practice with a higher rate of completeness. We recommend the BISAP score as a non-inferior, pragmatic risk stratification tool in acute pancreatitis.
HPB SO58 - Reporting outcomes on the management of complex benign biliary pathology referred into a tertiary Hepatobiliary centre
Authors: Mobarak Zina , Mobarak Shahd , Maugham Alison , Jamdar Saurabh
Published: November 2024

Background

Gallstone disease represents a significant portion of acute general surgery workload. Complex biliary pathology is a common cause of referrals to tertiary hepatobiliary (HPB) centres, however, there is a paucity in the literature regarding criteria for referrals and the outcomes from the management of these cases. The aim of this study was to report the outcomes of patients referred to a tertiary HPB centre in an acute setting from secondary care hospitals for management of benign biliary pathology.

Method

Patients who were transferred to the HPB unit at Manchester Royal Infirmary from secondary care hospitals in the North West of England between September 2022 and May 2024 for benign biliary pathology were included. Patients were identified from the electronic emergency transfer centre. Data was collected on the reason for referral and management at the HPB unit. Outcomes were reported as: admission to intensive care (ITU), length of stay in hospital, in-hospital mortality, Clavien-Dindo grading of surgical complications and re-admission to hospital. Data was retrospectively collected from electronic patient records.

Results

Twenty-three patients were included. The most common reasons for transfer included: biliary drainage for choledocholithiasis where endoscopic retrograde cholangiopancreatography (ERCP) was not feasible at the referring hospital (8/23); Mirizzi syndrome (4/23); emergency general surgery not offered at the referring hospital (3/23) and perforated gallbladder (2/23). Ten patients were managed surgically, five patients had ERCPs, four patients had radiological interventions and four were managed conservatively. Two patients were admitted to ITU, one patient died within admission and a second patient managed conservatively was re-admitted within 30 days. Post-operative morbidity rate was 30%. The median hospital stay was 12 days (2, 50).

Conclusion

Our data demonstrates that complex biliary pathology that has been referred into a tertiary HPB unit from secondary care hospitals has been managed safely, with low rates of morbidity and mortality. Patients who underwent cholecystectomies that were deemed to be high risk had a 0% mortality rate. This study adds to the body of evidence that centralisation of specialist services with a multi-disciplinary approach has led to better patient outcomes.
HPB SO77 - Effects of Patient and Operative Variables on Isolation of Primary Human Hepatocytes
Authors: Young Robert , Malik Hassan , Diaz-Nieto Rafael , Fenwick Stephen , Jones Robert , Copple Ian
Published: November 2024

Background

Isolation of human primary hepatocytes from tissue samples derived from therapeutic hepatectomy offers an important resource for a range of pharmacological and toxicology based experimental platforms, whilst simultaneously providing an opportunity to reduce the use of animal models. This study analysed the impact of a range of patient and operative derived variables on the yield and viability of isolated human primary hepatocytes.

Method

Excess hepatic tissue from resected liver parenchyma was sampled from consented patients undergoing major and minor hepatectomy for a range of oncological and non-oncological indications. Tissue dissociation and hepatocyte isolation was performed using a two-step collagenase perfusion procedure. Hepatocyte viability was calculated using the Trypan blue exclusion test while hepatocyte yield was calculated by the number of cells isolated divided by the tissue mass isolated from. Patient and operative variables were collected retrospectively from 25 patients in a prospectively maintained database.

Results

Samples from normal liver parenchyma achieved high hepatocyte viability and yields in all patients. Improved hepatoctye viability was associated with female sex, with a 2.9% increase in viability in samples from women (P<0.05). Patient age, BMI, operative indication, neo-adjuvant chemotherapy, as well as prolonged intra-operative Pringle time and blood loss did not significantly affect hepatocyte yield or viability, allowing use of primary human hepatocytes from a wide range of patients in a plethora of translational research experiments.

Conclusion

High levels of hepatocyte viability and yield are achievable across a broad range of patients, even in instances patients with high burdens of disease, prolonged Pringle time or higher levels of intra-operative blood loss. Tissue samples from consenting patients undergoing therapeutic liver resection provide an invaluable resource for various translational experimental platforms, including primary human hepatocytes. To date, more than 400 patients have donated tissue used in a range of basic science techniques, significantly reducing reliance on animal models.
Opa1 and MT-Nd6 mutations induce early mitochondrial changes in the retina and prelaminar optic nerve of hereditary optic neuropathy mouse models
Authors: Bureau Jacques , Manero Florence , Baris Olivier , Bodin Alexia , Verny Christophe , Chevrollier Arnaud , Lenaers Guy , Codron Philippe
Published: November 2024

Hereditary optic neuropathies, including dominant optic atrophy and Leber’s hereditary optic neuropathy, are genetic disorders characterized by retinal ganglion cell degeneration leading to vision loss, mainly associated with mitochondrial dysfunction. In this study, we analysed mitochondrial distribution and ultrastructure in the retina and longitudinal optic nerve sections of pre-symptomatic hereditary optic neuropathies mouse models with Opa1 and Nd6 deficiency to identify early mitochondrial changes. Our results show significant mitochondrial fragmentation and increased mitophagy in Opa1+/− mice, indicating early mitochondrial changes prior to neuronal loss. Conversely, Nd6P25L mice exhibited mitochondrial hypertrophy, suggesting an adaptive response to compensate for altered energy metabolism. These pre-symptomatic mitochondrial changes were mainly observed in the unmyelinated portion of the retinal ganglion cell axons, where the transmission of the visual information requires high energy expenditure, constituting the specific point of vulnerability in hereditary optic neuropathies. These findings highlight early focal mitochondrial changes prior to neuronal loss in hereditary optic neuropathies and provide insight into pre-symptomatic therapeutic approaches.
In-hospital Outcomes of Healthcare-associated Coronavirus Disease 2019 (Omicron) Versus Healthcare-associated Influenza: A Retrospective, Nationwide Cohort Study in Switzerland
Authors: Grant Rebecca , de Kraker Marlieke E A , Buetti Niccolò , Jackson Holly , Abbas Mohamed , Sobel Jonathan Aryeh , Sommerstein Rami , Eder Marcus , Balmelli Carlo , Troillet Nicolas , Schreiber Peter W , Jent Philipp , Senn Laurence , Flury Domenica , Tschudin-Sutter Sarah , Buettcher Michael , Süveges Maria , Urbini Laura , Keiser Olivia , Roder Ursina , Harbarth Stephan , Zanella Marie-Céline ,   for the CH-SUR Study Group, Berger Christoph , Bernhard-Stirnemann Sara , Cusini Alexia , Heininger Ulrich , Niederer-Loher Anita , Nussbaumer-Ochsner Yvonne , Stocker Reto , Vuichard-Gysin Danielle , Zimmermann Petra , Zucol Franziska
Published: November 2024

Background

As coronavirus disease 2019 (COVID-19) is integrated into existing infectious disease control programs, it is important to understand the comparative clinical impact of COVID-19 and other respiratory diseases.

Methods

We conducted a retrospective cohort study of patients with symptomatic healthcare-associated COVID-19 or influenza reported to the nationwide, hospital-based surveillance system in Switzerland. Included patients were adults (aged ≥18 years) hospitalized for ≥3 days in tertiary care and large regional hospitals. Patients had COVID-19 symptoms and a real-time polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection ≥3 days after hospital admission between 1 February 2022 and 30 April 2023, or influenza symptoms and a real-time polymerase chain reaction–confirmed influenza A or B infection ≥3 days after hospital admission between 1 November 2018 and 30 April 2023. Primary and secondary outcomes were 30-day in-hospital mortality and admission to intensive care unit, respectively. Cox regression (Fine-Gray model) was used to account for time dependency and competing events, with inverse probability weighting to adjust for confounding.

Results

We included 2901 patients with symptomatic, healthcare-associated COVID-19 (Omicron) and 868 patients with symptomatic, healthcare-associated influenza from 9 hospitals. We found a similar case fatality ratio between healthcare-associated COVID-19 (Omicron) (6.2%) and healthcare-associated influenza (6.1%) patients; after adjustment, patients had a comparable subdistribution hazard ratio for 30-day in-hospital mortality (0.91; 95% confidence interval, .67–1.24). A similar proportion of patients were admitted to the intensive care unit (2.4% COVID-19; 2.6% influenza).

Conclusions

COVID-19 and influenza continue to cause severe disease among hospitalized patients. Our results suggest that in-hospital mortality risk of healthcare-associated COVID-19 (Omicron) and healthcare-associated influenza are comparable.
PCDP-CRLPPM: a classified regional location privacy-protection model based on personalized clustering with differential privacy in data management
Authors: Shi Wenlong , Zhang Jing , Chen Xiaoping , Ye Xiucai
Published: November 2024

Location data management plays a crucial role in facilitating data collection and supporting location-based services. However, the escalating volume of transportation big data has given rise to increased concerns regarding privacy and security issues in data management, potentially posing threats to the lives and property of users. At present, there are two possible attacks in data management, namely Reverse-clustering Inference Attack and Mobile-spatiotemporal Feature Inference Attack. Additionally, the dynamic allocation of privacy budgets emerges as an NP-hard problem. To protect data privacy and maintain utility in data management, a novel protection model for location privacy information in data management, Classified Regional Location Privacy-Protection Model based on Personalized Clustering with Differential Privacy (PCDP-CRLPPM), is proposed. Firstly, a twice-clustering algorithm combined with gridding is proposed, which divides continuous locations into different clusters based on the different privacy protection needs of different users. Subsequently, these clusters are categorized into different spatiotemporal feature regions. Then, a Sensitive-priority algorithm is proposed to allocate privacy budgets adaptively for each region. Finally, a Regional-fuzzy algorithm is presented to introduce Laplacian noise into the centroids of the regions, thereby safeguarding users’ location privacy. The experimental results demonstrate that, compared to other models, PCDP-CRLPPM exhibits superior resistance against two specific attack models and achieves high levels of data utility while preserving privacy effectively.
Complete heart block and subsequent sudden cardiac death following transcatheter tricuspid valve replacement in a heart transplant patient: a case report
Authors: Jiang Andy , Davey Ryan , Tweedie Edward J , Smith Stuart J
Published: November 2024

Background

Tricuspid regurgitation (TR) is a common valvular complication following heart transplantation. Transcatheter tricuspid valve replacement exists as a novel treatment option. However, as with any procedure, important complications can occur and warrant discussion.

Case summary

A 46-year-old woman, status post-orthotopic heart transplant (HT), developed symptomatic severe TR. She underwent transcatheter tricuspid valve replacement (TTVR; EVOQUE system, Edwards Lifesciences) and was subsequently presented to the hospital following a syncopal event. She was found to be in cardiogenic shock with complete heart block on an electrocardiogram that degenerated into sudden cardiac death. Although the valve was well-seated, autopsy revealed areas of focal necrosis where the bioprosthetic valve was seated in the region of the atrioventricular node and His bundle.

Discussion

This is the first case report of a complication of transcatheter tricuspid valve replacement in a heart transplant patient resulting in complete heart block and sudden cardiac death. While TTVR may be a good treatment option for select patients in this high-risk group, conduction system damage is a potential complication given the anatomy of the region and requires very close monitoring. This case further highlights the unique physiology of HT patients and illustrates the fact that bradyarrhythmias are often poorly tolerated and potentially lethal.
Transitory Income Windfalls and Charitable Giving: Evidence from Norwegian Register Data, 1993–2021
Authors: Geys Benny , Sørensen Rune J
Published: November 2024

This paper studies the impact of unearned, transitory income shocks on charitable giving using Norwegian administrative data. We exploit the random timing and size of lottery wins and our long time period (1993–2021) to estimate both short- and longer-term impacts. We find no meaningful effect of small windfalls. Yet, windfalls exceeding $10,000 induce a long-lasting increase in the likelihood to donate, the absolute level of donations and the share of annual income donated (conditional on donating). We show that this is consistent with individuals thinking of large transitory income shocks as a long-term addition to their annual income.
Ligand distances as key predictors of pathogenicity and function in NMDA receptors
Authors: Montanucci Ludovica , Brünger Tobias , Bhattarai Nisha , Boßelmann Christian M , Kim Sukhan , Allen James P , Zhang Jing , Klöckner Chiara , Krey Ilona , Fariselli Piero , May Patrick , Lemke Johannes R , Myers Scott J , Yuan Hongjie , Traynelis Stephen F , Lal Dennis
Published: November 2024

Genetic variants in the genes GRIN1, GRIN2A, GRIN2B, and GRIN2D, which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic and neurodevelopmental disorders, including early onset epilepsy, developmental and epileptic encephalopathy, intellectual disability, and autism spectrum disorders. Missense variants in these genes can result in gain or loss of the NMDAR function, requiring opposite therapeutic treatments. Computational methods that predict pathogenicity and molecular functional effects of missense variants are therefore crucial for therapeutic applications. We assembled 223 missense variants from patients, 631 control variants from the general population, and 160 missense variants characterized by electrophysiological readouts that show whether they can enhance or reduce the function of the receptor. This includes new functional data from 33 variants reported here, for the first time. By mapping these variants onto the NMDAR protein structures, we found that pathogenic/benign variants and variants that increase/decrease the channel function were distributed unevenly on the protein structure, with spatial proximity to ligands bound to the agonist and antagonist binding sites being a key predictive feature for both variant pathogenicity and molecular functional consequences. Leveraging distances from ligands, we developed two machine-learning based predictors for NMDA variants: a pathogenicity predictor which outperforms currently available predictors and the first molecular function (increase/decrease) predictor. Our findings can have direct application to patient care by improving diagnostic yield for genetic neurodevelopmental disorders and by guiding personalized treatment informed by the knowledge of the molecular disease mechanism.
Genetic analysis implicates ERAP1 and HLA as risk factors for severe Puumala virus infection
Authors: Haapaniemi Hele , Strausz Satu , Tervi Anniina , Jones Samuel E , Kanerva Mari ,   FinnGen, Estonian Biobank Research Team, Abner Erik , Fors Connolly Anne-Marie , Ollila Hanna M
Published: November 2024

Puumala virus (PUUV) infections can cause severe illnesses such as Hemorrhagic Fever with Renal Syndrome in humans. However, human genetic risk factors contributing to disease severity are still poorly understood. Our goal was to elucidate genetic factors contributing to PUUV infections and understand the biological mechanisms underlying individual vulnerability to PUUV infections. Leveraging data from the FinnGen study, we conducted a genome-wide association study on severe Hemorrhagic Fever with Renal Syndrome caused by PUUV with 2227 cases. We identified associations at the Human Leukocyte Antigen (HLA) locus and ERAP1 with severe PUUV infection. HLA molecules are canonical mediators for immune recognition and response. ERAP1 facilitates immune system recognition and activation by cleaving viral proteins into smaller peptides which are presented to the immune system via HLA class I molecules. Notably, we identified that the lead variant (rs26653, OR = 0.84, P = 2.9 × 10–8) in the ERAP1 gene was a missense variant changing amino acid arginine to proline. From the HLA region, we showed independent and significant associations with both HLA class I and II genes. Furthermore, we showed independent associations with four HLA alleles with severe PUUV infection using conditional HLA fine mapping. The strongest association was found with the HLA-C*07:01 allele (OR = 1.54, P = 4.0 × 10−24) followed by signals at HLA-B*13:02, HLA-DRB1*01:01, and HLA-DRB1*11:01 alleles (P < 5 × 10−8). Our findings suggest an association of viral peptide processing with ERAP1 and antigen presentation through HLA alleles that may contribute to the development of severe PUUV disease.
Analysis of genotype effects and inter-individual variability in iPSC-derived trisomy 21 neural progenitor cells
Authors: Lee Sarah E , Baxter Laura L , Duran Monica I , Morris Samuel D , Mosley Iman A , Fuentes Kevin A , Pennings Jeroen L A , Guedj Faycal , Bianchi Diana W
Published: November 2024

Trisomy of human chromosome 21 (T21) gives rise to Down syndrome (DS), the most frequent live-born autosomal aneuploidy. T21 triggers genome-wide transcriptomic alterations that result in multiple atypical phenotypes with highly variable penetrance and expressivity in individuals with DS. Many of these phenotypes, including atypical neurodevelopment, emerge prenatally. To enable in vitro analyses of the cellular and molecular mechanisms leading to the neurological alterations associated with T21, we created and characterized a panel of genomically diverse T21 and euploid induced pluripotent stem cells (iPSCs). We subsequently differentiated these iPSCs to generate a panel of neural progenitor cells (NPCs). Alongside characterizing genotype effects from T21, we found that T21 NPCs showed inter-individual variability in growth rates, oxidative stress, senescence characteristics, and gene and protein expression. Pathway enrichment analyses of T21 NPCs identified vesicular transport, DNA repair, and cellular response to stress pathways. These results demonstrate T21-associated variability at the cellular level and suggest that cell lines from individuals with DS should not solely be analyzed as a homogenous population. Examining large cohorts of genetically diverse samples may more fully reveal the effects of aneuploidy on transcriptomic and phenotypic characteristics in T21 cell types.

A panel of genomically diverse T21 and euploid induced pluripotent stem cells (iPSCs) were created and subsequently differentiated into neural progenitor cells (NPCs). T21 NPCs showed reduced growth, increased oxidative stress, and inter-individual variability in gene and protein expression. This inter-individual variability suggests that studies with large cohorts of genetically diverse T21 samples may more fully reveal the effects of aneuploidy.
Biologics and Oral Small Molecules Are Not Associated With Increased Major Adverse Cardiovascular Events or Venous Thromboembolism in Inflammatory Bowel Disease
Authors: Qapaja Thabet , Abu-Rumaileh Mohammed , Alsabbagh Alchirazi Khaled , Gharaibeh Ahmad , Naser Ahmad , Hamid Osama , Alayan Dina , Regueiro Miguel
Published: November 2024

Background

Biologics and oral small molecules (OSM) effectively treat inflammatory bowel disease (IBD), but some are linked to higher risks of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE). This study evaluates the MACE and VTE risks in IBD patients treated with biologics or OSM.

Methods

Using the TrinNetX multi-institutional database, we examined MACE and VTE in adult IBD patients on biologics and compared them to IBD patients not on biologics. We also compared IBD patients on OSM to those not on OSM. We performed 1:1 propensity score matching. MACE (myocardial infarction [MI], stroke, and all-cause mortality) and VTE were assessed from 30 days to 3 years after drug prescription.

Results

After matching, IBD patients on biologics had reduced risk of MI, stroke, and all-cause mortality at 1 year, compared to those not on biologics (P < .05). No significant difference in VTE was observed (P = .5). At 3 years, biologic-treated patients had lower risks of MI, stroke, all-cause mortality, and VTE (P < .05). Inflammatory bowel disease patients on OSM showed no significant differences in MI, stroke, or VTE at 1 and 3 years, but had lower all-cause mortality (P < .05). In older IBD patients with at least 1 cardiovascular risk factor, OSM usage showed no significant difference in MI, stroke, or VTE risk compared to nonusers; however, all-cause mortality was decreased at 3 years (P < .05).

Conclusions

Inflammatory bowel disease patients treated with biologics or OSM were not at increased risk of MACE or VTE. Although further studies and longer follow-up periods are needed to confirm these findings, our results provide reassurance regarding the safety of these medications in IBD.
A re-assessment of Palaeotanyrhina (Hemiptera: Heteroptera) elucidates the phylogeny of Leptopodoidea
Authors: Rédei Dávid
Published: November 2024

A morphologically unusual fossil true bug genus, Palaeotanyrhina Poinar, Brown & Kóbor, 2022, placed into Cimicomorpha: Reduvioidea by its authors, is revisited based on an inclusion in mid-Cretaceous Burmese amber. The original description is supplemented with additional details and corrections. It is demonstrated that the placement of Palaeotanyrhina into Cimicomorpha was based on misinterpretations of the morphology of the holotype, and the genus is a member of the infraorder Leptopodomorpha. A phylogenetic analysis is provided for fossil and extant taxa of Leptopodomorpha. Parvilepta Yu, Zhuo & Chen, 2023, Cretaleptus Sun & Chen, 2019, Macrolepta Yu, Zhuo & Chen, 2023 (currently members of Leptopodidae: Leptosaldinae) and Palaeoleptus Poinar, 2009 (the type genus of Palaeoleptidae) are demonstrated to be phylogenetically closely related to Palaeotanyrhina. All the above mentioned genera are recognized to represent stem-group members of Leptopodomorpha: Leptopodidae: Leptopodinae: Leptopodini, and accordingly, they are transferred to the latter tribe. The following new subjective synonyms are proposed: Leptopodidae: Leptopodinae: Leptopodini Brullé, 1836 = Palaeoleptidae Poinar, 2009, syn. nov. = Palaeotanyrhinidae Poinar, Brown & Kóbor, 2022, syn. nov. Based on the analytic results, the subfamilies Leptosaldinae and Leptopodinae of Leptopodidae and the tribes Leotichiini and Leptopodini of Leptopodinae are considered valid, redefined, and a list of their included genera and species are provided. Arguments are provided in support of the placement of Leptosaldinea Popov & Heiss, 2016, formerly placed into Leptosaldinae, into the infraorder Dipsocoromorpha.
Archives of cyanobacterial traits: insights from resurrected Nodularia spumigena from Baltic Sea sediments reveal a shift in temperature optima
Authors: Medwed Cynthia , Karsten Ulf , Romahn Juliane , Kaiser Jérôme , Dellwig Olaf , Arz Helge , Kremp Anke
Published: November 2024

Cyanobacterial blooms in the Baltic Sea proliferated in recent decades due to rising sea surface temperatures, resulting in significant ecological impacts. To elucidate their current success, we examined ecophysiological, biochemical, and morphological traits of recent and ~33-year-old strains of Nodularia spumigena using a resurrection approach. The ability of many cyanobacteria to form dormant stages that can persist in anoxic sediments for decades provides a unique opportunity to study adaptive traits to past environmental conditions. A short sediment core from the Eastern Gotland Basin was processed to isolate strains of N. spumigena buried in 1987 ± 2 and 2020 ± 0.5 Common Era. Sequencing was used for species identification, followed by characterization of cell morphometry, carbon, nitrogen, and chlorophyll a content. Photosynthetic performance was evaluated by using pulse-amplitude modulated fluorimetry and oxygen optodes to assess light and temperature requirements. Our results revealed trait changes in N. spumigena over the past 3 decades: Temperature optimum for photosynthesis shifted from 15.3–21.1°C, which is consistent with the past and present local SST. Recent strains exhibited increased carbon, nitrogen, and chlorophyll a content despite decreased cell volume. The demonstrated adaptability of N. spumigena to increasing temperature suggests that this species will thrive in a warmer climate in the future. These insights will aid modeling efforts aimed at understanding and managing consequences of future cyanobacterial blooms in the Baltic Sea ecosystem.
Vancomycin combined with piperacillin/tazobactam increases the risk of acute kidney injury compared with vancomycin plus other anti-pseudomonal beta-lactams: a systematic review and network meta-analysis
Authors: Pan Kunming , Li Ranyi , Li Yanli , Ding Xiaoqiang , Li Xiaoyu , Lv Qianzhou
Published: November 2024

Objective

To explore whether vancomycin plus piperacillin/tazobactam actually increases nephrotoxicity compared with other anti-pseudomonal beta-lactams (BLs).

Methods

PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang and VIP were searched from inception to October 2023. The primary outcomes were acute kidney injury (AKI) as defined as acute increase in serum creatinine of 0.3 mg/dL or 50% and severe Stage 2–3 AKI.

Results

We included 70 studies (76 638 patients). Network meta-analysis indicated that vancomycin plus piperacillin/tazobactam was associated with significantly higher AKI risk than vancomycin plus cefepime (OR 2.55, 95% CI 2–3.28), vancomycin plus meropenem (OR 2.26, 95% CI 1.71–3.02) and vancomycin plus other uncommonly used BLs (OR 2.47, 95% CI 1.87–3.29). Also, vancomycin + piperacillin/tazobactam was associated with significantly higher Stage 2–3 AKI risk than vancomycin + cefepime (OR 2.22, 95% CI 1.34–3.62), vancomycin + meropenem (OR1.96, 95% CI 1.22–3.25) and vancomycin + uncommonly used BLs (OR 2.81, 95% CI 1.66–4.91). Vancomycin plus piperacillin/tazobactam did not result in a significant difference in the incidence of receiving dialysis treatment, mortality, length of stay and time to AKI. Subgroup analyses of studies conducting propensity score matching demonstrated vancomycin + piperacillin/tazobactam was associated with significantly higher AKI rates than vancomycin + cefepime (OR 2.19, 95% CI 1.38–3.47) and vancomycin + meropenem (OR 1.38, 95% CI. 1.18–1.60). Subgroup analysis of critically ill patients and children indicated that vancomycin + piperacillin/tazobactam was associated with significantly higher AKI rates.

Conclusions

Vancomycin + piperacillin/tazobactam significantly increased the risk of AKI and severe Stage 2–3 AKI compared with vancomycin plus other BLs. More prospective studies are needed.
An integrative approach to the taxonomy of Oxymycterus paramensis (Rodentia, Cricetidae) and related nominal forms
Authors: Jayat J Pablo , Torres Ricardo , D’Elía Guillermo , de Oliveira João A , Ortiz Pablo E , Teta Pablo
Published: November 2024

Oxymycterus includes 17 species of small- to medium-sized sigmodontine rodents. The taxonomy of this genus has been widely studied, but several unresolved issues persist. One example of this is the Paramo Hocicudo, Oxymycterus paramensis, which over its extended latitudinal range has been associated with several nominal forms that have not been evaluated with an integrative approach. Based on phylogenetic analyses of the Cytb gene, qualitative and quantitative morphological characters, and environmental niche modeling, we reexamined the taxonomic status of the nominal forms akodontius, jacentior, and paramensis while considering the recently recognized species O. willkaurco. The phylogenetic reconstruction guided subsequent analysis of morphological variation and the development of the niche models. Considering the results in an integrative framework, we observed congruence among phylogenetic, species distribution models, and environmental niche models (a proxy indicating different environmental preferences), which support the recognition of 2 species within the concept of O. paramensis s.l. At the same time, we did not observe congruent support for this taxonomic hypothesis from morphological evidence, with the absence of diagnostic qualitative or quantitative characters differentiating the 2 taxa. Considering that some lines of evidence suggest the interruption of gene flow, we see more support for recognizing existing names for 2 taxa at the species level: O. paramensis, endemic to Bolivia; and O. akodontius (which has priority over jacentior), distributed from southern Bolivia to northwestern Argentina. However, we recommend more detailed studies to test the taxonomic scenario advanced here.
Spatial stress analysis in an elastic parallelepiped
Authors: Tokovyy Yuriy , Yuzvyak Mykola
Published: November 2024

The direct integration method is extended onto the 3D analysis of an elastic rectangular parallelepiped subject to arbitrary force loadings on its sides. By making use of the equilibrium equations, the integral-form expressions are derived for the stress-tensor components through the introduced Vihak functions. These expressions were efficiently used to reduce the original sets of the local boundary conditions to the equivalent sets of the integral conditions for the Vihak functions. In such a manner, the original problems are managed to be reduced to the auxiliary boundary value problems for the governing integro-differential equations with accompanying integral conditions for the Vihak functions. For solving the auxiliary problems for the key functions, special semi-analytical algorithms are suggested in engaging a specific approach for the separation of variables by making use of the complete systems of orthogonal eigen- and associated functions. This allows for determining the Vihak key functions and, consequently, the stress-tensor components in the form of explicit analytical dependencies on the applied force loadings. The solution is quite beneficial for both theoretical and practical implementations. It was shown by the numerical evidence that the solutions are efficient for the analysis of stress fields in the entire domain including edges and corners.
Postcritical discourse analysis: examining the case of the student well-being discourse
Authors: Schwimmer Marina
Published: November 2024

This article examines how the critical tradition initiated by Nietzsche and pursued through poststructuralism might be compatible with what is currently being described as postcritique. It does so by looking at the example of critical discourse analysis (CDA). The first section gives some indications about the state of the methodology currently known as critical discourse analysis and introduces what a ‘postcritical’ reaction could look like. The second section focuses on a concrete example and presents the main critical literature about the student well-being discourse, showing that it generally limits itself to a debunking attitude. The third section explores how the affirmative and creative dimension of critique, its ‘postcritical’ dimension, has been and could be put forward to contribute to what could be called a postcritical discourse analysis methodology
A model estimating the level of floral transition in olive trees exposed to warm periods during winter
Authors: Smoly Ilan , Elbaz Haim , Engelen Chaim , Wechsler Tahel , Elbaz Gal , Ben-Ari Giora , Samach Alon , Friedlander Tamar
Published: November 2024

Rising winter temperatures jeopardize the fruit yield of trees that require a prolonged and sufficiently cold winter to flower. Predicting the exact risk to different crop varieties is the first step in mitigating the harmful effects of climate change. This work focused on olive (Olea europaea)—a traditional crop in the Mediterranean basin in which flowering depends on the sufficiency of cold periods and the lack of warm ones during the preceding winter. A satisfactory quantitative model forecasting its expected flowering under natural temperature conditions is still lacking. The effect of different temperature regimes on olive flowering level and flowering gene expression was tested empirically. A modified ‘dynamic model’ describing the response of a putative flowering factor to the temperature signal was constructed. The crucial component of the model was an unstable intermediate, produced and degraded at temperature-dependent rates. The model accounts for the number of both cold and warm hours and also for their sequence. Empirical flowering and temperature data were applied to fit the model parameters, using numerical constrained optimization techniques; the model outcomes were successfully validated. The model accurately predicted low-to-moderate flowering under winters with warm periods and properly accounted for the effects of warm periods during winter.
Digital Dark Field—Higher Contrast and Greater Specificity Dark Field Imaging Using a 4DSTEM Approach
Authors: MacLaren Ian , Fraser Andrew T , Lipsett Matthew R , Ophus Colin
Published: November 2024

A new method for dark field imaging is introduced, which uses scanned electron diffraction (or 4DSTEM—4-dimensional scanning transmission electron microscopy) datasets as its input. Instead of working on simple summation of intensity, it works on a sparse representation of the diffraction patterns in terms of a list of their diffraction peaks. This is tested on a thin perovskite film containing structural ordering resulting in additional superlattice spots that reveal details of domain structures, and is shown to give much better selectivity and contrast than conventional virtual dark field imaging. It is also shown to work well in polycrystalline aggregates of CuO nanoparticles. In view of the higher contrast and selectivity, and the complete exclusion of diffuse scattering from the image formation, it is expected to be of significant benefit for characterization of a wide variety of crystalline materials.
The impact of the cosmological constant on past and future star formation
Authors: Sorini Daniele , Peacock John A , Lombriser Lucas
Published: November 2024

We present an extended analytical model for cosmic star formation, with the aim of investigating the impact of cosmological parameters on the star formation history within the $\Lambda$CDM paradigm. Constructing an ensemble of flat $\Lambda$CDM models where the cosmological constant varies between $\Lambda = 0$ and $10^5$ times the observed value, $\Lambda _{\rm obs}$, we find that the fraction of cosmic baryons that are converted into stars over the entire history of the universe peaks at $\sim$ 27 per cent for $0.01 \lesssim \Lambda /\Lambda _{\rm obs} \lesssim 1$. We explain, from first principles, that the decline of this asymptotic star formation efficiency for lower and higher values of $\Lambda$ is driven, respectively, by the astrophysics of star formation, and by the suppression of cosmic structure formation. However, the asymptotic efficiency declines slowly as $\Lambda$ increases, falling below 5 per cent only for $\Lambda \gt 100 \, \Lambda _{\rm obs}$. Making the minimal assumption that the probability of generating observers is proportional to this efficiency, and following Weinberg in adopting a flat prior on $\Lambda$, the median posterior value of $\Lambda$ is $539 \, \Lambda _{\rm obs}$. Furthermore, the probability of observing $\Lambda \le \Lambda _{\rm obs}$ is only 0.5 per cent. Although this work has not considered recollapsing models with $\Lambda \lt 0$, the indication is thus that $\Lambda _{\rm obs}$ appears to be unreasonably small compared to the predictions of the simplest multiverse ensemble. This poses a challenge for anthropic reasoning as a viable explanation for cosmic coincidences and the apparent fine-tuning of the Universe: either the approach is invalid or more parameters than $\Lambda$ alone must vary within the ensemble.
Depolarization and Faraday effects in AGN Jets
Authors: Yushkov E , Pashchenko I N , Sokoloff D , Chumarin G
Published: November 2024

Radio interferometric observations of active galactic nuclei (AGN) jets reveal the significant linear polarization of their synchrotron radiation that changes with frequency due to the Faraday rotation. It is generally assumed that such depolarization could be a powerful tool for studying the magnetized plasma in the vicinity of the jet. However, depolarization could also occur within the jet if the emitting and rotating plasma are cospatial (i.e. the internal Faraday rotation). Burn obtained very simple dependence of the polarization on the wavelength squared for the discrete source and resolved slab that is widely used for interpreting the depolarization of AGN jets. However, it ignores the influence of the non-uniform large-scale magnetic field of the jet on the depolarization. Under the simple assumptions about the possible jet magnetic field structures, we obtain the corresponding generalizations of Burn’s relation widely used for galaxies analysis. We show that the frequency dependences of the Faraday rotation measure and polarization angle in some cases allow to estimate the structures of the jets magnetic fields.
The ultraviolet luminosity function of star-forming galaxies between redshifts of 0.4 and 0.6
Authors: Page M J , Dwelly T , McHardy I , Seymour N , Mason K O , Sharma M , Kennea J A , Sasseen T P , Breeveld A A , Matthews A E
Published: November 2024

We combine ultraviolet imaging of the $13^{H}$ survey field, taken with the XMM–Newton Optical Monitor telescope (XMM–OM) and the Neil Gehrels Swift Observatory Ultraviolet and Optical Telescope (UVOT) in the UVM2 band, to measure rest-frame ultraviolet 1500 Å luminosity functions of star-forming galaxies with redshifts z between 0.4 and 0.6. In total the UVM2 imaging covers a sky area of 641 arcmin$^{2}$, and we detect 273 galaxies in the UVM2 image with $0.4\lt z\lt 0.6$. The luminosity function is fit by a Schechter function with best-fitting values for the faint end slope $\alpha =-1.8^{+0.4}_{-0.3}$ and characteristic absolute magnitude $M^{*} = -19.1^{+0.3}_{-0.4}$. In common with XMM–OM based studies at higher redshifts, our best-fitting value for $M^{*}$ is fainter than previous measurements. We argue that the purging of active galactic nuclei from the sample, facilitated by the cospatial X-ray survey carried out with XMM–Newton is important for the determination of $M^{*}$. At the brightest absolute magnitudes ($M_{1500}\lt -18.5$), the average UV colour of our galaxies is consistent with that of minimal-extinction local analogues, but the average UV colour is redder for galaxies at fainter absolute magnitudes, suggesting that higher levels of dust attenuation enter the sample at absolute magnitudes somewhat fainter than $M^{*}$.