bluuebunny/crossref_metadata_2025 huggingface dataset:
A214 CONSTRUCTION AND VALIDATION OF A FRAILTY INDEX FOR THE INFLAMMATORY BOWEL DISEASE POPULATION
Authors: Willett N , Stewart S , Jones J , Theou O , Rockwood K
Published: February 2025

Background

Frailty can be defined as a state of vulnerability to adverse health events, resulting from a reduction in physiological processes that are protective for health. Measuring frailty in populations with chronic immune-mediated disease, such as Inflammatory Bowel Disease (IBD), is becoming increasingly important. A Frailty Index (FI) operates within the Deficits Accumulation model and is a valid and accepted method of measuring frailty. Much of the work done in the field of frailty and IBD describes the association of frailty with post-operative complications and mortality. These studies have used various methods to determine a patient’s degree of frailty such as use of ICD codes and claims-based scoring.

Aims: Aims

To develop an FI for the IBD patient population using an accumulation of deficits approach.

Methods

A standardized method for constructing an FI using data from the SPOR IMAGINE IBD cohort was applied to a pan-Canadian, observational prospective study. Seventy-seven deficits were selected to be incorporated into the index, most from psychological or gastrointestinal variables. Construct and content validity of the index was assessed. The index was trichotomized based on established cut points and was then compared to patient demographics in the baseline cohort.

Results

An IBD Frailty Index (FI) was created using a validated 10 step process with baseline data from 2714 participants in the SPOR IMAGINE cohort. The IBD FI is made up of 77 items, and is primarily composed of physical, functional and psychological health deficits. The IBD FI showed a right skew, which is characteristic of most FIs. In this distribution the upper limit (99th percentile) of FI score is 0.529 displaying a submaximal limit, and the mean FI score was higher in women (0.19) (95% CI: 0.13, 0.15] compared to men (0.14), which are characteristic to valid FI tools. The mean age of our cohort was 45.8 years (SD: 15), mean FI score was 0.17 (SD: 0.12) (lower than in other immune mediated diseases), and 30.6% of our sample was categorized as frail (FI score >0.21). Surprisingly the IBD FI scores were not positively associated with age, though they were associated with IBD symptom severity (R=0.767).

Conclusions

Frailty is an important health measure that provides a holistic picture of an individual’s health. We operationalized the accumulation of deficits approach to frailty and created a frailty measurement tool for the IBD population using variables from a wide variety of health domains. Future research projects using the IBD FI should investigate the scores’ predictive abilities for mortality and should explore the differences in frailty between patients diagnosed in middle of life (first epidemiological peak) versus later in life.

Funding Agencies

None
A215 INJECTION SITE PAIN AND ADHERENCE IN PATIENTS SWITCHING FROM REFERENCE ADALIMUMAB TO AVT02 – INTERIM RESULTS OF THE EASE PAIN TRIAL.
Authors: Shahrokh D K , Afif W , Steinhart A , Narula N
Published: February 2025

Background

AVT02, a biosimilar to reference product (RP) adalimumab, was first approved in Canada in 2022. AVT02 is formulated at high concentration and with citrate-free excipients. The EASE PAIN trial is a Phase IV study in Canada evaluating the impact of switching from RP, or an alternative adalimumab biosimilar, to AVT02.

Aims

The primary objective was to examine the impact of switching on injection site pain across patients in Canada. Secondary objectives included describing the impact of switching on injection site reaction including burning sensation and soreness, treatment adherence, and patient-reported quality of life.

Methods

The study enrolled patients with gastrointestinal conditions (Crohn’s disease [CD], ulcerative colitis [UC]), rheumatological conditions (rheumatoid arthritis [RA], ankylosing spondylitis [AS], psoriatic arthritis [PsA]), or dermatological conditions (hidradenitis suppurativa [HS], psoriasis [PsO]). Participants were eligible if their treating physician had decided to switch them from low-concentration RP or alternative adalimumab biosimilar to AVT02. The study assesses injection site pain measured via Visual Analog Scale (VAS), adherence, and quality of life (based on EQ-5D-5L) for participants up to Day 180 after switching. The study is currently ongoing (331 Patients enrolled in the Study; 287 included in the interim analysis)

Results

The intention-to-treat (ITT) population comprised 287 participants. Following the first administration of AVT02, injection site VAS pain score decreased by an average of -18.8 ± 25.51 across the whole population. Supporting this, there was reduction in overall injection site reactions (49.1%), burning sensation (79.4%), and soreness (84.8%) between baseline (RP administration) and follow-up (AVT02 administration). Adherence rate was 95.5% overall. The ITT population maintained high quality of life score (EQ-5D-5L score of >81 on a scale of 1-100) after switching from RP to AVT02.

Conclusions

The results of this study demonstrate that switching from RP or alternative biosimilar adalimumab to AVT02 leads to decreased injection site pain across all indications, and maintenance of high adherence rates and high quality of life among patients.

Funding Agencies

None
A233 CANADIAN EXPERIENCE OF ENDOSCOPIC ULTRASOUND-GUIDED GALLBLADDER DRAINAGE: A CASE SERIES
Authors: Jiang S X , Thilakanathan C , Winter R , Byrne M F , Jain A , Motomura D , Gan S , Trasolini R
Published: February 2025

Background

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an emerging treatment for acute cholecystitis in patients who are poor surgical candidates. There is a lack of EUS-GBD data in the Canadian setting, which may differ from its global counterparts in pattern of healthcare availability, aging population, and use of conscious sedation.

Aims

To describe outcomes following EUS-GBD in the Canadian setting.

Methods

The case series included patients undergoing EUS-GBD by an interventional gastrointestinal endoscopist in a tertiary academic centre in Canada. Data included were clinicodemographic information, procedural details, and clinical outcomes.

Results

From September 2023 to September 2024, a total of 18 patients underwent EUS-GBD. Median age was 85 (IQR 75-88) years, 6 (33%) were female, and 17 (94%) were American Society of Anesthesiologists Physical Status (ASA) classification III. Indication included 15 cases of acute calculous cholecystitis and 3 (17%) cases of salvage treatment for malignant biliary obstruction without alternative access. Placement was transduodenal in 10 (56%) and transgastric in 8 (44%). A coaxial double pigtail was placed in 15 cases (83%). Conscious sedation was used for 15 cases (83%), with 1 case using deep sedation with propofol and 2 with general anesthesia. All cases were technically successful followed by improvement of symptoms and biochemistry. There were no intra-procedural complications, but 3 post-procedural complications were noted. One patient had recurrent cholecystitis after 1 month due to stent occlusion despite coaxial pigtail placement, which was managed endoscopically with symptom resolution. Another patient had a buried stent, which was managed with placement of a second lumen-apposing metal stent within the first stent. A third patient had pain post-procedure suspected due to stent expansion, which self-resolved within 2 weeks. No rescue percutaneous or surgical interventions were required following EUS-GBD. No patients underwent subsequent cholecystectomy. Four patients died from underlying systemic disease, including 3 patients who underwent EUS-GBD for malignant obstruction with no recurrent cholecystitis up to time of death at 15-150 days post-procedure.

Conclusions

In an elderly population and using primarily conscious sedation, EUS-GBD was safe and effective in patients with high surgical risk, underscoring the suitability of this technique for a Canadian setting.

A. Gallbladder with debris/sludge on EUS. B. Distal flange of lumen apposing metal stent (LAMS) deployed within gallbladder lumen. C. Proximal flange deployed in duodenum. D. Coaxial double pigtail placed within LAMS.

Funding Agencies

None
A234 ELEVATED DIRECT BILIRUBIN DOES NOT PREDICT ELEVATED CONJUGATED BILIRUBIN IN NEONATES
Authors: Samaraweera P , Brill H
Published: February 2025

Background

Neonatal cholestasis guidelines consider direct and conjugated bilirubin to be equivalent because the delta bilirubin component of direct bilirubin is assumed to be negligible. Since 2015 William Osler Health System automatically measures conjugated bilirubin if the direct bilirubin is 20 µmol/L or greater in patients under 3 months old. This afforded us the opportunity to assess if direct bilirubin accurately reflects conjugated bilirubin.

Aims

To determine if direct bilirubin reliably reflects conjugated bilirubin levels in neonates and confirms the appropriateness of further investigation of neonatal cholestasis

Methods

Patient data from 2015 to 2024 was retrospectively collected and analyzed, focusing on neonates three months or younger with direct bilirubin levels of 20 µmol/L or higher. Both Direct and Conjugated bilirubin were measured using different assays. Main outcome measure was the difference between direct and conjugated bilirubin measurements.

Results

Results: 121 subjects were identified. Average direct bilirubin (32.0µmol/L) and average conjugated bilirubin (8.9µmol/L) are significantly different (p=0.008). A direct bilirubin below 22 µmol/L almost never results in a conjugated bilirubin above 2 µmol/L. Moreover, for a conjugated bilirubin of 17 or higher (the guideline trigger for neonatal cholestasis investigations), the lowest direct bilirubin measured was 34.

Conclusions

Direct Bilirubin is not an analogous proxy for conjugated bilirubin. Future guidelines should be modified to require confirming cholestasis with a conjugated bilirubin if direct bilirubin is the default tes

Funding Agencies

None
A237 INCIDENCE, RISK FACTORS, AND OUTCOMES OF POST-ERCP CHOLANGITIS: AN INTERNATIONAL MULTICENTER PROSPECTIVE STUDY
Authors: Gupta M , Fazal M , Hammal J , Ficaccio S , Khan R , Forbes N
Published: February 2025

Background

Cholangitis is a well-described adverse event (AE) following endoscopic retrograde cholangiopancreatography (ERCP) that is associated with significant morbidity and mortality. Despite this, contemporary characterization of this AE using high-quality prospective data is incomplete.

Aims

In this study we describe post-ERCP cholangitis incidence, risk factors, and outcomes in a large, international multicenter population of patients undergoing ERCP.

Methods

We analyzed prospective data from nine centers in Canada, USA, and Europe between 2018-2024 with 30-day follow-up. The primary outcome was post-ERCP cholangitis, defined as (1) temperature <36.0°C or >38.0°C or white blood cells <4 x109/L or >10x109/L, (2) accompanying rise in bilirubin or transaminases to >1.5 times the upper limit of normal or any increase compared to pre-procedure, and (3) emergency department visit or hospital admission and/or prolongation of existing admission. Multivariable logistic regression was performed to identify risk factors, with results presented as odds ratios (OR) with associated 95% confidence intervals. Outcomes following cholangitis were also described.

Results

Post-ERCP cholangitis occurred following 134 (1.7%) of 8,119 ERCPs (mean onset of symptoms 2.0 days). Repeat ERCP was required in 53.7% of these cases. Mortality attributed to cholangitis occurred in 8.2% of incident cases. Male sex (OR 1.48, 1.02-2.19), longer procedural time (OR 1.01, 1.00-1.02 per additional minute) and presence of a biliary stricture (OR 3.24, 1.98-5.30) were all independent risk factors for post-ERCP cholangitis, while placement of a biliary stent (OR 0.59, 0.36-0.95), and biliary sphincterotomy (OR 0.59 0.39-0.87) were both protective against post-ERCP cholangitis.

Conclusions

Post-ERCP cholangitis is common and associated with high mortality rates. Adequate pre-procedural counseling and early recognition is advised, especially in patients at increased risk.

Funding Agencies

None
A238 A MULTIDISCIPLINARY APPROACH FOR PANCREATICOBILIARY CANCER WITH EMPHASIS ON TIME TO CARE ACCESS: AN OVERVIEW OF THE EDMONTON PANCREATICOBILIARY INFLAMMATION AND CANCER (EPIC) PROGRAM
Authors: Ashrafinia N , Timmermans M , Buchanan G , Perryman S , Kwan A , Bereznicki E , Mathura P , Sandha G
Published: February 2025

Background

Persistent challenges in pancreaticobiliary (PB) cancer management continue to have a significant impact on patients. Prolonged access to care, for diagnosis and treatment, prompted the launch of a multidisciplinary approach in 07/2023 to provide timely access to patient-centred points of care, and to improve overall quality of life (QOL).

Aims

To evaluate the outcomes of the multidisciplinary EPIC program, with a focus on access to care timelines established in a collaborative care pathway developed for this program.

Methods

All consecutive patients with suspected PB cancer presenting to the University of Alberta Hospital between 07/2023 and 08/2024 were referred to the EPIC program. Referrals were triaged by gastroenterology, pancreaticobiliary surgery, and the EPIC nurse navigator (NN) into resectable, partially resectable, and unresectable cases. Endoscopic intervention for biopsy and/or stent placement was scheduled as necessary, and referral to the local cancer cantre when indicated. Appropriate referrals were made to palliative and dietary services. The NN ensured timely referral and scheduling in accordance with the care pathway timelines and served as the primary point of contact for patients throughout their journey. Data was entered into the REDCap database. Descriptive statistics were performed.

Results

A total of 254 patients (152 male, 102 female) with a median age of 68±11 years were referred. Presenting symptoms were abdominal/back pain (72%), weight loss (47%), jaundice (36%), nausea/vomiting (18%), pruritus (9%), coincidental finding (6%), new-onset diabetes (6%), and fever (1%). The site of cancer was pancreas (81%), bile duct (13%), ampulla (2%), and others 3%. The median times to access are shown in the table and figure. The 6- and 12-month survival for resectable pancreatic cancer was 93% and 82%, respectively, whereas for unresectable pancreatic cancer was 44% and 37%, respectively.

Conclusions

A NN-led, patient-centred care model is crucial for timely access to care in PB cancer. Improved coordination of care and overall improvement in patient QOL were demonstrated with the initiation of this program.

TIME TO CARE ACCESS IN DAYS, median ± SD

Funding Agencies

None
A245 THE ROLE OF FODMAP-MICROBIOTA INTERACTIONS IN IBS-RELATED VISCERAL PAIN
Authors: Ables S E , Bennett A S , Vanner S J , Lomax A E , Reed D E
Published: February 2025

Background

Irritable bowel syndrome (IBS) is characterized by abdominal pain and altered bowel habits. IBS is more common in females. Furthermore, food and stress are two common triggers of abdominal pain in IBS patients. A low FODMAP diet (LFD) reduces abdominal pain in a subgroup of IBS patients, although the mechanism behind this is unclear. We hypothesize that a LFD improves abdominal pain by altering neuroactive gut luminal mediators.

Aims

1. Explore the effect of a LFD on IBS symptoms and gut luminal mediator-induced neuronal activity.

2. Investigate whether stress alters IBS symptoms and luminal mediator-induced neuronal activity.

3. Examine sex differences in dorsal root ganglion (DRG) neuron sensitivity to luminal mediators.

Methods

Six female IBS patients followed a LFD for six weeks. Participants donated stool samples and completed the IBS Symptom Severity Scale (IBS-SSS) and the Depression, Anxiety, and Stress Scale (DASS-21) questionnaires. Male and female C57Bl6 mouse DRG neurons were incubated with IBS patient and healthy control (HC) fecal supernatant (FS). Capsaicin-induced Ca2+ influx was quantified to measure neuronal activity. N refers to number of mice.

Results

Overall, IBS FS collected prior to the LFD caused a 17% increase in neuronal activity compared to HC FS (N=32 mice, p<0.05). This finding was sex dependent, as only DRG neurons from female mice exhibited an IBS FS-induced increase in neuronal activity (N=18, p<0.005). There was no difference in neuronal activity caused by IBS FS versus HC FS in neurons from male mice (N=16, p>0.05). FS collected from patients after a LFD did not alter neuronal activity compared to FS collected before the LFD (N=32, p>0.05). However, when solely analyzing neurons from female mice, LFD FS-induced neuronal activity was lower than IBS FS-treated neuronal activity (N=16, p<0.05).

Four IBS patients reported a clinically significant improvement in symptoms (>50-point reduction in IBS-SSS scores) during the LFD. Of these, two had a >50% reduction in IBS-SSS scores and their LFD FS reduced neuronal activity compared to their IBS FS (N=10, p<0.05). The two others had modest symptom improvement on the LFD; their LFD FS had similar effect on neuronal activity compared to their IBS FS (N=11, p>0.05). Additionally, in two IBS patients, periods of severe stress (DASS-21 stress sub-scale score >26) corresponded to high IBS-SSS scores; FS from these time points increased neuronal activity (N=10, p<0.05).

Conclusions

In a subgroup of IBS patients, a LFD improves symptoms and reduces the excitatory effects of luminal mediators on sensory neuronal activation. Stress appears to increase the excitatory effects of luminal mediators and exacerbates IBS symptoms. Finally, neurons from female mice may be more sensitive to pro-nociceptive luminal mediators, potentially contributing to abdominal pain in female IBS patients.

Funding Agencies

CIHR
A248 ETHANOL-INDUCED MUCOSAL IRRITATION DISRUPTS LOCAL AND SYSTEMIC PROTECTIVE EFFECTS OF NON-INVASIVE TRANSCUTANEOUS AURICULAR VAGUS NERVE STIMULATION (TAVNS)
Authors: Hesampour F , Bernstein C N , Ghia J
Published: February 2025

Background

The integrity of the mucosal barrier is vital for gastrointestinal homeostasis. Previously, we demonstrated that non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) decreases inflammatory and pro-apoptotic markers while increasing anti-inflammatory markers in homeostatic conditions. However, its effectiveness in case of slight mucosal irritation remains unclear.

Aims

To assess whether slight mucosal irritation affects taVNS efficacy in modulating pro- and anti-inflammatory cytokines and apoptosis-related markers in the colon and spleen.

Methods

Male C57BL/6 mice were given a single intrarectal dose of 30% ethanol (ETOH group, 100 µl), while the control (CTRL) group received no ethanol. Preventive taVNS (10V, 20Hz & 500us, 10min/day) or no stimulation (clipping only) began one day before ethanol injection and continued for four days. Colonic and splenic levels of interleukin (IL)-10, tumor growth factor (TGF)-β, tumor necrosis factor (TNF)-α, pro-apoptotic markers Bcl-2-associated X protein (BAX), Bcl-2 homologous antagonist killer (BAK1), caspase8, and pro-survival BCL2 associated agonist of cell death (BAD) were measured using qRT-PCR and ELISA.

Results

taVNS significantly increased IL-10 mRNA expression (p<0.0001) and both mRNA (p<0.015) and protein (p<0.0001) levels of TGF-β in CTRL conditions, with no changes in the ETOH group. Mice demonstrated unchanged IL-10 protein levels in the colon in the presence or absence of taVNS. However, in CTRL conditions, taVNS downregulated BAX (p<0.0001), BAK1(p<0.0001), and caspase8 (p<0.0002) mRNA expression significantly, with no effect in the ETOH group. Additionally, BAD (p<0.0001) mRNA expression increased significantly in CTRL conditions but remained unchanged in the ETOH group. In the spleen, taVNS decreased TNF-α (p<0.04) and increased TGF-β (p<0.0007) protein levels in CTRL conditions without impacting the ETOH group.

Conclusions

Our findings demonstrated that taVNS successfully regulated systemic and local cytokines and apoptosis-related markers in control mice. However, a slight irritation induced by ethanol abolished its effects, indicating that ethanol associated with a slight mucosa irritation can modify the taVNS outcome.

Funding Agencies

CIHR
A250 ESOPHAGOGASTRIC JUNCTION OUTFLOW OBSTRUCTION SECONDARY TO METASTATIC SQUAMOUS CELL CARCINOMA A CASE REPORT AND REVIEW OF THE LITERATURE
Authors: Alhashimalsayed Z , McIntosh K
Published: February 2025

Background

Esophagogastric junction outflow obstruction (EGJOO) is a condition characterized by impaired relaxation of the lower esophageal sphincter, with intact peristalsis. The Chicago Classification version 4.0 (CCv4.0) updated the diagnostic criteria to include not only elevated integrated relaxation pressure (IRP) but also dysphagia, high intrabolus pressure, and abnormal findings on timed barium esophagram or FLIP. EGJOO can be caused by secondary factors such as structural issues, medications, inflammatory conditions, or cancer, with rare cases linked to metastatic disease, like SCC of the skin. Identifying metastatic cancer as a potential cause in motility disorders requires careful evaluation in unusual cases

Aims

A 63-year-old man with a two-month history of dysphagia, 20-pound weight loss, chest pressure, and regurgitation did not respond to PPIs. His medical history included type 2 diabetes, two renal transplants, and a past cutaneous squamous cell carcinoma (SCC) treated with surgery and radiotherapy. He was on long-term immunosuppressive therapy. Endoscopy showed a tightly constricted LES, and HRM confirmed EGJOO with impaired LES relaxation. CT imaging revealed an 8 cm mass at the gastroesophageal junction and a 4 cm lung lesion. Biopsy confirmed metastatic SCC, indicating recurrence. This case emphasizes the need to consider malignancy in EGJOO, especially in patients with cancer history and immunosuppression

Methods

N

Results

EGJOO secondary to metastatic SCC is rare but important to recognize. Diagnostic criteria in CCv4.0 help reduce false positives by incorporating symptoms and confirmatory tests, differentiating clinically significant EGJOO from incidental findings. It is crucial to systematically evaluate for secondary causes, particularly malignancy, though routine imaging may not provide additional benefits over endoscopy and timed barium esophagram unless there is a strong suspicion

This case highlights how a history of SCC and long-term immunosuppression can contribute to metastasis to the GEJ. Management primarily focuses on palliative care to relieve dysphagia and enhance quality of life, using endoscopic, pharmacological, or radiotherapy options, while more invasive treatments like POEM or pneumatic dilation may be less appropriate for cancer patients

Conclusions

This case report highlights a rare cause of EGJOO secondary to metastatic SCC, emphasizing the need for thorough evaluation in dysphagia cases. Findings suggest that cancer should be considered in EGJOO patients with known cancer histories or immunosuppression. Early recognition and palliative management can significantly enhance the patient’s quality of life by effectively addressing dysphagia. This report contributes to the understanding of EGJOO as a heterogeneous condition with various underlying pathologies, including metastatic cancer

Funding Agencies

None
Disease-modifying anti-nephropathic drugs (DMANDs) – A definition proposed by the Immunonephrology Working Group (IWG) of the European Renal Association (ERA)
Authors: Teng Y K Onno , Frangou Eleni , Kronbichler Andreas , Bruchfeld Annette , Caravaca-Fontan Fernando , Floege Jürgen , Moran Sarah M , Mirioglu Safak , Stevens Kate I , Steiger Stefanie , Romagnani Paola , Anders Hans-Joachim
Published: February 2025

A definition of “disease modification“ for kidney disease is long overdue. Here, we propose three key criteria for disease modification in immune-mediated glomerulonephritis and podocytopathies: minimizing disease activity, preventing loss of kidney structure and function, and reducing treatment-related toxicity. To be considered a DMAND, a drug must fulfil all three criteria hence, the DMAND status of a drug may not be clear at the time of regulatory approval. Notably, the aspect of CKD in immune-mediated kidney diseases must be considered and treated separately, e.g., RASi is a DMAND for the CKD aspect but not for the immune disease itself. Defining DMANDs is an ambitious goal but one which may help to set the priorities for future treatment strategies in immune-mediated kidney disease. This may mean much more rapid tapering or even avoidance of unselective, non-targeted immunosuppressive agents, which carry considerable short (teratogenicity) and long term risks (malignancies). The criteria proposed here set a high bar for “disease modification” in immune-mediated kidney disease. Inevitably, this must dictate altered priorities with the focus for new therapeutic agents and strategies shifting from solely reduction of proteinuria to preservation of GFR and attenuation of decline, whilst also eliminating long term toxicity.
A pretrained transformer model for decoding individual glucose dynamics from continuous glucose monitoring data
Authors: Lu Yurun , Liu Dan , Liang Zhongming , Liu Rui , Chen Pei , Liu Yitong , Li Jiachen , Feng Zhanying , Li Lei M , Sheng Bin , Jia Weiping , Chen Luonan , Li Huating , Wang Yong
Published: February 2025

Continuous glucose monitoring (CGM) technology has grown rapidly to track real-time blood glucose levels and trends with improved sensor accuracy. The ease of use and wide availability of CGM would facilitate safe and effective decision making for diabetes management. Here, we developed an attention-based deep learning model, CGMformer, pretrained on a well-controlled and diverse corpus of CGM data to represent individual's intrinsic metabolic state and enable clinical applications. During pretraining, CGMformer encodes glucose dynamics including glucose level, fluctuation, hyperglycemia, and hypoglycemia into latent space with self-supervised learning. It shows generalizability in imputing glucose value across five external datasets with different populations and metabolic states (MAE=3.7 mg/dl). We then finetuned CGMformer towards a diverse panel of downstream tasks in the screening of diabetes and complications using task-specific data, which demonstrated a consistently boosted predictive accuracy over direct fine-tuning on a single task (AUROC=0.914 for T2D screening and 0.741 for complication screening). By learning an intrinsic representation of individual's glucose dynamics, CGMformer classify non-diabetic individuals into six clusters with elevated T2D risks, and identify a specific cluster with lean body-shape but high risk of glucose metabolism disorders, which is overlooked by traditional glucose measurements. Furthermore, CGMformer achieves high accuracy in predicting individual's postprandial glucose response with dietary modelling (Pearson correlation coefficient=0.763) and helps personalized dietary recommendation. Overall, CGMformer pretrains a transformer neural network architecture to learn an intrinsic representation by borrowing information from a large amount of daily glucose profiles, demonstrates predictive capabilities fine-tuning towards a broad range of downstream applications, and holds promise in early warning of T2D and recommendation for lifestyle modification in diabetes management.
Atomic force microscopy imaging of plant cell walls
Authors: Pu Junbao , Ma Jie , Zhai Hang , Wu Shanshan , Wang Youmei , Putnis Christine V , Wang Lijun , Zhang Wenjun
Published: February 2025

Plant cell walls are highly dynamic, complex structures composed of multiple biopolymers that form a scaffold surrounding the plant cell. A nanoscale understanding of their architecture, mechanical properties, and formation/degradation dynamics is crucial for revealing structure–function relationships, mechanisms of shape formation, and cell development. Although imaging techniques have been extensively used in recent decades to reveal the structural organization and chemical compositions of cell walls, observing the detailed native architecture and identifying the physicochemical properties of plant cell walls remains challenging. Atomic force microscopy (AFM) is a powerful tool for simultaneously characterizing the morphology, nanomechanical properties, single-molecule interactions, and surface potentials of living biological systems. However, studies employing AFM to investigate plant cell walls have been relatively scarce. In this review, we discuss the latest advancements in AFM for in situ imaging of the multidimensional structure of the cell wall, measuring the mechanical properties of plant tissues or single cells, specific single-molecule recognition of cell wall-related enzymes-polysaccharides, and detecting the Kelvin potential of plant cell walls. We emphasize the fundamental challenges of AFM in characterizing plant cell walls and review potential applications for state-of-the-art AFM-based infrared/Raman spectroscopy toward answering open questions in plant biology.
Leaf minimum conductance dynamics during and after heat stress: Implications for plant survival under hotter droughts
Authors: Fernandes Viviane de Araújo Brito , Farnese Fernanda Santos , Arantes Brenner Ryan , Fontineles da Silva Maria Lúcia , Silva Fabiano Guimarães , Torres-Ruiz José M , Slot Martijn , Cochard Hervé , Menezes-Silva Paulo Eduardo
Published: February 2025

Exposure to temperatures above a critical threshold (temperature of phase transition, Tp) can damage the leaf cuticle, leading to increased leaf minimum conductance (gleaf-res). Despite the implications of increased gleaf-res for species survival under hotter-drought conditions, little is known about the dynamics of gleaf-res variation after heatwave episodes. Here, we examined the gleaf-res variation before, during, and after exposure to high temperatures (HTs) in a group of representative Cerrado tree species. Through multiple experiments, we compared gleaf-res in leaves previously exposed to different temperatures for varying durations with leaves not submitted to HT. Leaves previously exposed to temperatures above Tp and subsequently cooled had higher gleaf-res measured at 25 °C than leaves not exposed to HT, suggesting a “thermal leaky legacy” effect that negatively impacted plant survival under contrasting simulated drought scenarios. This legacy effect was induced by short periods of heat stress and increased proportionally with rising temperatures. Notably, increased gleaf-res was observed even after 24 h of leaf storage, evidencing that thermal-induced damages to the leaf cuticle cannot be fully repaired within a daily cycle. Overall, our study highlights the threats that increased gleaf-res during and after heatwaves may pose to plant performance and survival under drought conditions and emphasizes the importance of considering the dynamic nature of such water leaks to improve the predictions of drought-induced mortality events in a warmer and drier world.
Understanding the social burden of multiple sclerosis patients in Georgia: a comprehensive analysis of quality of life and sociodemographic factors
Authors: Khutsishvili Natalia , Ganugrava Nino , Janelidze Marina , Vashadze Tamar , Kiziria Marina , Megrelishvili Marika , Tsiskaridze Alexander
Published: February 2025

Background and objectives

Multiple sclerosis (MS) is a chronic autoimmune disorder that significantly impacts individuals’ quality of life and imposes a substantial social burden on patients and society. Despite its global socioeconomic implications, limited research has focused on the social burden of MS. This study aimed to assess the social burden of MS in Georgia by evaluating the health-related quality of life of MS patients and exploring the correlation between disease burden and quality of life.

Methodology

This cross-sectional study was performed to assess the social burden of the disease by evaluating the impact of the disease on the quality of life of 384 patients with MS. The Multiple Sclerosis Quality of Life-54 questionnaire was administered to assess quality of life.

Results

The Expanded Disability Status Scale score was significantly negatively correlated with the physical health composite score (r = −0.249, P < .001) and the general quality of life score (r = −0.220, P < .001). The quality of life was highly associated with gender, employment status, living/residence place, and moderately with age.

Conclusions and implications

This study revealed the intricate interplay between disability, quality of life, and sociodemographic factors among Georgian MS patients. The results of the study highlight the need for specialized therapies, networks of support, and public health initiatives to lessen the societal cost of MS.
Driving change: Exploring cattle transporters’ perspectives to improve worker and animal well-being
Authors: Sullivan Paxton A , Varnum Angela , Bigler Libby , Cramer M Caitlin , Román-Muñiz I Noa , Edwards-Callaway Lily N
Published: February 2025

The cattle industry has made considerable efforts to adopt more sustainable beef production practices. Still, the social pillar of sustainability—especially workforce well-being—often receives less attention than the environmental and economic pillars. There is also limited information about the perspectives of U.S. cattle transporters, who play a critical role in ensuring animal welfare during the final stages of the beef supply chain. This study explored cattle transporters’ perspectives on management practices related to cattle care and well-being, training, work environment, and community. Cattle transporters (N = 74) from three trucking companies operating in Colorado, Kansas, Nebraska, and Texas participated in focus group discussions and completed a short, written survey. In total, 12 focus groups were conducted. In the written survey, 98.7% (n = 73) of survey respondents agreed with the statement “I have pride in the job I do,” and 97.3% (n = 72) agreed with the statement “Animal well-being is a critical component of my job.” Additionally, 96% (n = 71) of respondents agreed with the statement, “The training I have received at this job has prepared me well for transporting cattle,” highlighting the success of current education and training programs. Thematic analysis of focus group transcripts identified ten themes, including (1) Animal Welfare and Safety; (2) Feelings; (3) Human Welfare and Safety; (4) Learning and Training; (5) Money; (6) Opportunities for Improvement Throughout the Supply Chain; (7) Pride, Responsibility, and Care in Job; (8) Specialized Knowledge, Skills, and Commitment; (9) Unique, Positive Characteristics of the Job; and (10) Work Environment. Transporters expressed a strong sense of pride and responsibility in their work and viewed their role as essential to ensuring the well-being of cattle during transportation. However, they also identified several challenges, including ensuring human and animal safety, dealing with inadequate facilities, and a lack of cohesion among different supply chain sectors. As vital links between supply chain sectors, transporters offer unique insights. Listening to their daily observations could lead to improvements in operational efficiency and cattle welfare.
Analysis of travel decision behaviour during extreme floods in Pakistan
Authors: Talpur Aqsa , Baig Farrukh , Pervez Amjad , Lee Jaeyoung Jay
Published: February 2025

Extreme weather events like floods, exacerbated by climate change, disrupt transportation systems and endanger safety of the travellers. This study investigates how public perceptions of travel risks influence travel decisions during floods in Pakistan. In the context of urban floods and transportation, this study focuses on the perceived probability of a crash, perceived distraction, perceived security, perceived need for a companion, and perceived possibility of getting stuck in a traffic congestion, affecting people's travel decisions during floods. A questionnaire survey was conducted in Pakistan after the 2022 floods. Results from the data analysis of 526 valid responses indicated that. Furthermore, public perceptions varied in different flooding scenarios influenced by familiarity, available information, and road conditions. The study suggests real-time information sharing to ensure security, targeted education, and training to enhance community resilience against floods, development of guidelines for shelter camps on roadsides, and ensuring availability of public transport and ride-sharing services during floods may help to fulfil the public's mobility needs. Study findings will help to develop disaster risk management strategies to promote safe travels, improve urban planning for flood resilience, and guide post-disaster recovery efforts.
Differences in Outcomes for Patients Receiving Labetalol and Nicardipine for Hypertension After Craniotomy
Authors: Owrey Matthew , Sun George , Torjman Marc , Min Kevin J.
Published: February 2025

Background:

Acute postoperative hypertension (APH) is encountered in patients following craniotomy and is associated with major complications. This retrospective cohort study evaluates 30-day survival for patients who received labetalol, nicardipine, or both drugs.

Methods:

Patients 18 and older who underwent craniotomy between January 1, 2010 and January 1, 2023 were included in the study. Analyses were performed comparing (1) labetalol cohort versus nicardipine cohort, (2) labetalol cohort versus both cohort, and (3) nicardipine cohort versus both cohort. The primary outcome was survival at 30 days. Secondary outcomes included 30-day readmission, ST-elevation myocardial infarction (STEMI), congestive heart failure (CHF), non-ST elevation myocardial infarction (NSTEMI), arrhythmia, and intracranial hemorrhage.

Results:

The labetalol cohort had improved 30-day survival compared with the nicardipine cohort (HR: 0.49, P<0.0001) or both (HR: 0.67, P<0.0001). The nicardipine cohort had worse survival compared with both cohorts (HR: 1.28, P<0.0001). The labetalol cohort had a lower risk of intracranial hemorrhage compared with nicardipine (RR: 0.89, P=0.001) and both cohorts (RR: 0.90, P<0.001). The labetalol cohort had less congestive heart failure than the nicardipine cohort (RR: 0.66, P<0.0001), and the nicardipine cohort had more CHF than the cohort that received both drugs (RR: 1.21, P=0.018). There was no difference in STEMI, NSTEMI, or readmissions across cohorts.

Conclusions:

Labetalol for APH after craniotomy is associated with improved survival compared with nicardipine or combination. A combination of these drugs is associated with improved survival compared with nicardipine alone.
Chiari Malformation
Authors: Costa Francesco , Ait Benali Said , Dantas Fernando , Restelli Francesco , Mazzapicchi Elio , Baeesa Saleh , Yaman Onur , Sharif Salman , Alves Oscar L. , Zileli Mehmet , Botelho Ricardo
Published: February 2025

Study Design.

A comprehensive search was conducted in PubMed/EMBASE/MEDLINE databases. Inclusion criteria included publications between January 2011 and December 2022 on CM diagnosis classification, natural history, and conservative management.

Objective:

This study aims to offer an update on diagnosis classifications, natural history, and conservative management in Chiari Malformation (CM).

Summary of Background Data.

Chiari Malformation type 1 involves cerebellar tonsil herniation leading to neurological symptoms. There is controversy regarding its pathophysiology and optimal management, especially for asymptomatic cases. Previous research has focused on surgical outcomes with limited consensus on conservative strategies. Standardized guidelines are needed to enhance clinical decision-making.

Methods.

The screening process involved reviewing abstracts, assessing full-text articles, and reviewing references. Eligibility criteria ensured the selection of relevant studies. Data extraction involved recording various variables. Results were discussed and voted in two consensus meetings of the WFNS Spine Committee, reaching consensus using the Delphi method.

Results.

A total of 164 abstracts were screened. 99 articles met the inclusion criteria and were included in the study. Headache, brainstem and/or cerebellar/brainstem symptoms/signs were confirmed as the main typical neurological hallmarks of CM. Still, an accurate clinical assessment appeared to be the most reliable evaluation model available. Considering classification, the most common form in adult is type 1, while type 2 is associated with myelo-meningocele and hydrocephalus from childhood. MRI is the gold standard to show extent of tonsillar herniation, overcrowded posterior fossa or the absence of cisterna magna. Focusing on natural history, for asymptomatic or mildly symptomatic radiologically positive patients a conservative management is appropriate. Somato-sensory, motor, brainstem auditory evoked potentials and polysomnography could be helpful to guide eventual surgical indication.

Conclusion.

Further higher-quality studies are recommended to establish more substantial evidence and recommendations.
Syndromic Atlanto-axial Instability
Authors: Oertel Joachim , Uriza Gustavo , Radtke Karen , Lee June Ho , Costa Francesco , Dantas Fernando , Sharif Salman , Parthiban Jutty , Visocchi Massimiliano , Klekamp Jörg , Zileli Mehmet , Botelho Ricardo , Alves Óscar L.
Published: February 2025

Study Design.

Systematic review plus expert opinion framed on Delphi Method.

Objective.

Define criteria to on (i) how to screen for instability of cranio-vertebral CVJ in a high-risk population, especially in Down or Morquio syndrome, (ii) if or when which surgical procedure is indicated and (iii) whether syndromic patients can safely participate in sports activities.

Summary Background Data.

Syndromic abnormalities of CVJ may lead to potentially devastating neurological deficits. As of now, there is no international consensus on how to handle syndromic patients with atlanto-axial instability.

Methods.

International spine specialists of the WFNS spine committee reviewed statements from articles published between 2012 and 2022 to reach an expert agreement. Each statement was voted for on a Likert scale. The Delphi method was used to achieve a high level of validity.

Results.

Due to the high incidence of craniovertebral instability in Down’s patients, close neurological and radiological screening is advocated. In Morquio’s patients older than 5 years, it is recommended to perform an annual neurological examination and imaging studies to detect cervical stenosis or instability. For atlanto-axial instability (AAI), the recommended screening should include cervical spine lateral radiograph in controlled flexion/extension projections. In asymptomatic Down’s and Morquio syndrome patients with proven AAI, preventive stabilization might be considered. Neurological symptoms deriving from AAI are an indication for stabilization through Goel-Harms C1-C2 technique.

Patients without AAI and intact neurological status are cleared to unrestricted sports. Down syndrome patients with symptoms but without AAI or spinal cord compression can participate in most Special Olympics sports competition activities

Conclusions.

Consent was achieved on treatment recommendations for patients with syndromic disorders of the CVJ, with special focus laid on participation in physical activity and sports competitions. This should help spine surgeons and sports medicine doctors decide on a management path for each individual patient.
Impact of In-Hospital Bleeding on Post-Discharge Therapies and Prognosis in Acute Coronary Syndromes.
Authors: Spadafora Luigi , Betti Matteo , D’Ascenzo Fabrizio , De Ferrari Gaetano , De Filippo Ovidio , Gaudio Carlo , Collet Carlos , Sabouret Pierre , Agostoni Pierfrancesco , Zivelonghi Carlo , Pernice Bianca , Sarto Gianmarco , Simeone Beatrice , Rocco Erica , Russo Federico , Giordano Salvatore , Pierucci Nicola , Testa Alberto , Cacciatore Stefano , Biondi-Zoccai Giuseppe , Bernardi Marco
Published: February 2025

Acute coronary syndromes (ACS) continue to pose significant challenges for clinical practitioners, particularly regarding the prediction of mid- to long-term outcomes. This study aims to investigate the impact of in-hospital bleeding (IHB) at one-year follow-up in patients admitted for ACS. Data from 23,270 patients enrolled in the international PRAISE registry and discharged after ACS were analyzed. A total of 1,060 patients experienced IHB, while 18,765 did not; 3,445 were excluded due to missing data. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included major bleeding, reinfarction, and composite endpoints at 1 year. Patients with IHB were older, more frequently female, and had a higher prevalence of cardiovascular risk factors (all p < 0.05). At discharge, IHB patients were less likely to receive optimal medical therapy. At the one-year follow-up, all-cause mortality, major bleeding, and reinfarction were significantly higher in the IHB group (all p < 0.001). Bivariate analysis showed a strong association between IHB and all the outcomes of interest (all OR > 1; all p < 0.001). These associations remained significant even after adjusting for several covariates, except for reinfarction (OR 1.3; 95% CI 0.9–2.11; p = 0.149). Age, female sex, hypertension, and peripheral artery disease were found to be independent predictors of IHB, while DES implantation, radial access and left ventricular ejection fraction were identified as protective factors. IHB is a hallmark of frailty in ACS patients; therefore, greater attention should be given during follow-up to patients experiencing this condition.
Breast Cancer Occurrence After Risk-reducing Mastectomies in 274 Cases: A Single Center With More Than 42 Years of Experience
Authors: Patzelt Matej , Livancova Tereza , Le Thanh Xuan , Rosetzka Kristyna , Drozd Jan , Sukop Andrej
Published: February 2025

Introduction:

Carriers of genetic mutations with a high risk of developing breast cancer have a lifetime risk of this cancer of up to 70%. To reduce the risk, patients have the option of a risk-reducing mastectomy. There is limited data with only short follow-ups on its safety. The aim of the study was to determine the long-term incidence of breast cancer in healthy patients with no previous surgery, who underwent bilateral risk-reducing mastectomies (BRRMs).

Methods:

We retrospectively reviewed 274 patients from our facility with no previous breast surgery, who underwent BRRM from 1981 to 2022, due to genetic mutations, a strong family history, or having very dense mammary glands. We approached these patients during their checkups, by phone call or email, and we asked them if they had developed breast cancer after their procedures. We recorded the patients’ demographic factors, their genetic mutation types, and the mastectomy methods carried out.

Results:

A total of 274 patients had BRRMs with a mean follow-up after 76 months; 208 patients had undergone nipple-sparing mastectomies, 39 patients had undergone skin-sparing mastectomies, and 27 patients had skin-reducing mastectomies. One BRCA1+ patient developed breast cancer 21 months after undergoing the risk-reducing skin-sparing mastectomy procedure. None of the patients died of breast cancer.

Conclusions:

The incidence of breast cancer in the monitored patients is comparable to the results of the other related studies. The study result confirms that risk-reducing mastectomies reduce the risk of breast cancer in high-risk populations, regardless of the type of mastectomy performed.